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  • 201.
    Schmidt, Amand F.
    et al.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England..
    Swerdlow, Daniel I.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;Imperial Coll London, Dept Med, Fac Med, London, England..
    Holmes, Michael V.
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Epidemiol Studies Unit CTSU, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England..
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England.;St Bartholomews Hosp, Barts Heart Ctr, London, England..
    Fairhurst-Hunter, Zammy
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Lyall, Donald M.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Hartwig, Fernando Pires
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, Brazil..
    Horta, Bernardo Lessa
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, Brazil..
    Hypponen, Elina
    Univ South Australia, Ctr Populat Hlth Res, Sansom Inst Hlth Res, Adelaide, SA, Australia.;UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London, England.;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    Power, Christine
    UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London, England..
    Moldovan, Max
    Univ South Australia, Sch Hlth Sci, Adelaide, SA, Australia.;EMBL Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    van Iperen, Erik
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.;Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands..
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands..
    Demuth, Ilja
    Charite Univ Med Berlin, Charite Res Grp Geriatr, Berlin, Germany.;Charite Univ Med Berlin, Inst Med & Human Genet, Berlin, Germany..
    Norman, Kristina
    Charite Univ Med Berlin, Charite Res Grp Geriatr, Berlin, Germany..
    Steinhagen-Thiessen, Elisabeth
    Charite Univ Med Berlin, Charite Res Grp Geriatr, Berlin, Germany..
    Demuth, Juri
    E CA Econ GmbH, Berlin, Germany..
    Bertram, Lars
    Imperial Coll London, Neuroepidemiol & Ageing Res Unit, Fac Med, London, England.;Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Inst Neurogenet, Lubeck, Germany.;Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Inst Integrat & Expt Genom, Lubeck, Germany..
    Liu, Tian
    Max Planck Inst Human Dev, Berlin, Germany.;Max Planck Inst Mol Genet, Berlin, Germany..
    Coassin, Stefan
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol Innsbruck, Innsbruck, Austria..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Willeit, Karin
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Mason, Dan
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England..
    Wright, John
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England..
    Morris, Richard
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England..
    Wanamethee, Goya
    UCL, Dept Primary Care & Populat Hlth, London, England..
    Whincup, Peter
    St Georges Univ London, Populat Hlth Res Inst, London, England..
    Ben-Shlomo, Yoav
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England..
    McLachlan, Stela
    Univ Edinburgh, Ctr Populat Hlth Sci, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Price, Jackie F.
    Univ Edinburgh, Ctr Populat Hlth Sci, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Kivimaki, Mika
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Welch, Catherine
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Sanchez-Galvez, Adelaida
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Marques-Vidal, Pedro
    Univ Lausanne Hosp, Dept Med, Internal Med Unit, Lausanne, Switzerland..
    Nicolaides, Andrew
    Imperial Coll London, Dept Vasc Surg, Fac Med, London, England.;Univ Nicosia, Nicosia Med Sch, Dept Surg, Nicosia, Cyprus..
    Panayiotou, Andrie G.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus..
    Onland-Moret, N. Charlotte
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Matullo, Giuseppe
    Human Genet Fdn, Turin, Italy.;Univ Turin, Dept Med Sci, Turin, Italy..
    Fiorito, Giovanni
    Human Genet Fdn, Turin, Italy.;Univ Turin, Dept Med Sci, Turin, Italy..
    Guarrera, Simonetta
    Human Genet Fdn, Turin, Italy.;Univ Turin, Dept Med Sci, Turin, Italy..
    Sacerdote, Carlotta
    San Giovanni Battista Hosp, Canc Epidemiol Unit, Turin, Italy.;CPO Piemonte, Ctr Oncol Prevent, Turin, Italy..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Scott, Robert
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Bobak, Martin
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Malyutina, Sofi A.
    Novosibirsk State Med Univ, Novosibirsk, Russia.;Russian Acad Med Sci, Inst Internal & Prevent Med, Siberian Branch, Novosibirsk, Russia..
    Pajak, Andrzej
    Jagiellonian Univ, Coll Med, Krakow, Poland..
    Kubinova, Ruzena
    Natl Inst Publ Hlth, Prague, Czech Republic..
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Pikhart, Hynek
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Husemoen, Lise Lotte Nystrup
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Simonsen, Kenneth Starup
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Cooper, Jackie
    UCL, Ctr Cardiovasc Genet, London, England..
    Humphries, Steve E.
    UCL, Ctr Cardiovasc Genet, London, England..
    Brilliant, Murray
    Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA..
    Kitchner, Terrie
    Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA..
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA..
    Carrell, David S.
    Grp Hlth Res Inst, Seattle, WA USA..
    McCarty, Catherine A.
    Essentia Inst Rural Hlth, Duluth, MN USA..
    Kirchner, H. Lester
    Geisinger Med Clin, Ctr Hlth Res, Danville, PA USA..
    Larson, Eric B.
    Grp Hlth Res Inst, Seattle, WA USA..
    Crosslin, David R.
    Grp Hlth Res Inst, Seattle, WA USA..
    de Andrade, Mariza
    Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA..
    Roden, Dan M.
    Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.;Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA..
    Denny, Joshua C.
    Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA..
    Carty, Cara
    George Washington Univ, Washington, DC USA..
    Hancock, Stephen
    Univ Newcastle, Newcastle, NSW, Australia..
    Attia, John
    Univ Newcastle, Newcastle, NSW, Australia..
    Holliday, Elizabeth
    Univ Newcastle, Newcastle, NSW, Australia..
    Donnell, Martin O'
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Chong, Michael
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    van der Harst, Pim
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Said, M. Abdullah
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Eppinga, Ruben N.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Christen, Tim
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Pazoki, Raha
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Franco, Oscar
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Uitterlinden, Andre
    Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Dehghan, Abbas
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Biostat & Epidemiol, London, England.;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Baumeister, Sebastian
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Lerch, Markus M.
    Univ Med Greifswald, Dept Med A, Greifswald, Germany..
    Voelker, Uwe
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Ward, Joey
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Pell, Jill P.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Smith, Daniel J.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Meade, Tom
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England..
    Maitland-van der Zee, Anke H.
    Acad Med Ctr, Dept Resp Med, Amsterdam, Netherlands.;Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands..
    Baranova, Ekaterina V.
    Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands..
    Young, Robin
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Grobbee, Diederick E.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Froguel, Philippe
    Imperial Coll London, Fac Med, Dept Genom Common Dis, London, England.;Univ Lille, Inst Pasteur Lille, EGID, CNRS,UMR 8199, Lille, France..
    Thuillier, Dorothee
    Univ Lille, Inst Pasteur Lille, EGID, CNRS,UMR 8199, Lille, France..
    Balkau, Beverley
    INSERM, U1018, Ctr Rech Epidemiol & Sante Populat CESP, Renal & Cardiovasc Epidemiol, Villejuif, France..
    Bonnefond, Amelie
    Imperial Coll London, Fac Med, Dept Genom Common Dis, London, England.;Univ Lille, Inst Pasteur Lille, EGID, CNRS,UMR 8199, Lille, France..
    Cariou, Bertrand
    Univ Nantes, CHU Nantes, Inst Thorax, INSERM,CNRS, Nantes, France..
    Smart, Melissa
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Bao, Yanchun
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Kumari, Meena
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Ridker, Paul M.
    Harvard Med Sch, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA USA..
    Chasman, Daniel I.
    Harvard Med Sch, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA USA..
    Reiner, Alex P.
    Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Seattle, WA 98195 USA..
    Lange, Leslie A.
    Univ Colorado, Anschutz Med Campus, Denver, CO 80202 USA..
    Ritchie, Marylyn D.
    Geisinger Hlth Syst, Biomed & Translat Informat, Danville, PA USA.;Penn State Univ, Huck Inst Life Sci, Dept Biochem & Mol Biol, University Pk, PA 16802 USA..
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands..
    Casas, Juan-Pablo
    UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England..
    Keating, Brendan J.
    Univ Penn, Dept Surg, Philadelphia, PA 19104 USA..
    Preiss, David
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Epidemiol Studies Unit CTSU, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England..
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England..
    Sattar, Naveed
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study2017Inngår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, nr 2, s. 97-105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.

  • 202. Scott, R. A.
    et al.
    Pasko, D.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Yaghootkar, H.
    Barker, A.
    Sharp, S. J.
    Walker, M.
    Wareham, N. J.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Frayling, T.
    Langenberg, C.
    A genetic risk score comprising common variants associated with fasting insulin is associated with OGTT- and clamp-based indices of whole body insulin sensitivity2013Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S144-S145Artikkel i tidsskrift (Annet vitenskapelig)
  • 203. Scott, Robert A
    et al.
    Chu, Audrey Y
    Grarup, Niels
    Manning, Alisa K
    Hivert, Marie-France
    Shungin, Dmitry
    Tönjes, Anke
    Yesupriya, Ajay
    Barnes, Daniel
    Bouatia-Naji, Nabila
    Glazer, Nicole L
    Jackson, Anne U
    Kutalik, Zoltán
    Lagou, Vasiliki
    Marek, Diana
    Rasmussen-Torvik, Laura J
    Stringham, Heather M
    Tanaka, Toshiko
    Aadahl, Mette
    Arking, Dan E
    Bergmann, Sven
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Bornstein, Stefan R
    Brunner, Eric
    Bumpstead, Suzannah J
    Brage, Soren
    Carlson, Olga D
    Chen, Han
    Chen, Yii-Der Ida
    Chines, Peter S
    Collins, Francis S
    Couper, David J
    Dennison, Elaine M
    Dowling, Nicole F
    Egan, Josephine S
    Ekelund, Ulf
    Erdos, Michael R
    Forouhi, Nita G
    Fox, Caroline S
    Goodarzi, Mark O
    Grässler, Jürgen
    Gustafsson, Stefan
    Hallmans, Göran
    Hansen, Torben
    Hingorani, Aroon
    Holloway, John W
    Hu, Frank B
    Isomaa, Bo
    Jameson, Karen A
    Johansson, Ingegerd
    Jonsson, Anna
    Jørgensen, Torben
    Kivimaki, Mika
    Kovacs, Peter
    Kumari, Meena
    Kuusisto, Johanna
    Laakso, Markku
    Lecoeur, Cécile
    Lévy-Marchal, Claire
    Li, Guo
    Loos, Ruth J F
    Lyssenko, Valeri
    Marmot, Michael
    Marques-Vidal, Pedro
    Morken, Mario A
    Müller, Gabriele
    North, Kari E
    Pankow, James S
    Payne, Felicity
    Prokopenko, Inga
    Psaty, Bruce M
    Renström, Frida
    Rice, Ken
    Rotter, Jerome I
    Rybin, Denis
    Sandholt, Camilla H
    Sayer, Avan A
    Shrader, Peter
    Schwarz, Peter E H
    Siscovick, David S
    Stancáková, Alena
    Stumvoll, Michael
    Teslovich, Tanya M
    Waeber, Gérard
    Williams, Gordon H
    Witte, Daniel R
    Wood, Andrew R
    Xie, Weijia
    Boehnke, Michael
    Cooper, Cyrus
    Ferrucci, Luigi
    Froguel, Philippe
    Groop, Leif
    Kao, W H Linda
    Vollenweider, Peter
    Walker, Mark
    Watanabe, Richard M
    Pedersen, Oluf
    Meigs, James B
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Barroso, Inês
    Florez, Jose C
    Franks, Paul W
    Dupuis, Josée
    Wareham, Nicholas J
    Langenberg, Claudia
    No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels2012Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 61, nr 5, s. 1291-1296Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

  • 204. Scott, Robert A
    et al.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pasko, Dorota
    Barker, Adam
    Sharp, Stephen J
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Barroso, Inês
    Boeing, Heiner
    Clavel-Chapelon, Françoise
    Crowe, Francesca L
    Dekker, Jacqueline M
    Fagherazzi, Guy
    Ferrannini, Ele
    Forouhi, Nita G
    Franks, Paul W
    Gavrila, Diana
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Grioni, Sara
    Groop, Leif C
    Kaaks, Rudolf
    Key, Timothy J
    Kühn, Tilman
    Lotta, Luca A
    Nilsson, Peter M
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quirós, J Ramón
    Rolandsson, Olov
    Roswall, Nina
    Sacerdote, Carlotta
    Sala, Núria
    Sánchez, María-José
    Schulze, Matthias B
    Siddiq, Afshan
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke Mw
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L
    Yaghootkar, Hanieh
    McCarthy, Mark I
    Semple, Robert K
    Riboli, Elio
    Walker, Mark
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Frayling, Tim M
    Savage, David B
    Langenberg, Claudia
    Wareham, Nicholas J
    Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independently of obesity2014Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, nr 12, s. 4378-4387Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterise their association with intermediate phenotypes, and to investigate their role in T2D risk among normal-weight, overweight and obese individuals.We investigated the association of genetic scores with euglycaemic-hyperinsulinaemic clamp- and OGTT-based measures of insulin resistance and secretion, and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs-per-allele [95%CI]:-0.03[-0.04,-0.01];p=0.004). This score was associated with lower BMI (-0.01[-0.01,-0.0;p=0.02) and gluteofemoral fat-mass (-0.03[-0.05,-0.02;p=1.4x10-6), and with higher ALT (0.02[0.01,0.03];p=0.002) and gamma-GT (0.02[0.01,0.03];p=0.001). While the secretion score had a stronger association with T2D in leaner individuals (pinteraction=0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI- or waist-strata(pinteraction>0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.

  • 205.
    Scott, Robert A.
    et al.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Scott, Laura J.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Maegi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Marullo, Letizia
    Univ Ferrara, Dept Life Sci & Biotechnol, Ferrara, Italy..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Stanford Univ, Dept Genet, Stanford, CA USA..
    Kaakinen, Marika
    Imperial Coll London, Dept Genom Common Dis, London, England..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Pers, Tune H.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Boston Childrens Hosp, Div Endocrinol, Ctr Basic & Translat Obes Res, Boston, MA USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Johnson, Andrew D.
    Natl Heart Lung & Blood Inst, Div Intramural Res, Framingham Heart Study Populat Sci Branch, Framingham, MA USA..
    Eicher, John D.
    Natl Heart Lung & Blood Inst, Div Intramural Res, Framingham Heart Study Populat Sci Branch, Framingham, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Lee, Yeji
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Ma, Clement
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Steinthorsdottir, Valgerdur
    Amgen Inc, DECODE genet, Reykjavik, Iceland..
    Thorleifsson, Gudmar
    Amgen Inc, DECODE genet, Reykjavik, Iceland..
    Qi, Lu
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Van Zuydam, Natalie R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Chen, Han
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Human Genet Ctr & Dept Epidemiol, Human Genet Environm Sci, Houston, TX USA.;Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Sch Biomed Informat, Ctr Precis Hlth, Houston, TX USA..
    Almgren, Peter
    Lund Univ, Univ Hosp Scania, Dept Clin Sci Malmo, Lund Univ Diabet Ctr, Lund, Sweden..
    Voight, Ben F.
    Univ Penn sylvania, Perelman Sch Med, Dept Pharm, Philadelphia, PA USA.;Univ Pennsylvania, Perelman Sch Med, Dept Genet, Philadelphia, PA USA.;Univ Pennsylvania, Perelman Sch Medi cine, Inst Translat Med & Therapeut, Philadelphia, PA USA..
    Grallert, Harald
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Univ Hosp Grosshadern, Ludwig Maximilians Univ, Dep Med I, Munich, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Genet Epidemiol, Biometry & Epidemiol, Munich, Germany.;Munich Heart Alliance, German Ctr Cardiovascular Dis, Munich, Germany..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Rayner, Nigel W.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Karssen, Lennart C.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Polyomica S Hertogenbosch, Amsterdam, Netherlands..
    Van Leeuwen, Elisabeth M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Willems, Sara M.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Fuchsberger, Christian
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Chanda, Pritam
    Johns Hopkins Univ Sch Med, High Throughput Biol Ctr, Baltimore, MD USA..
    Li, Man
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Lu, Yingchang
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA.;Icahn Sch Med, Genet Obes & Related Metab Traits Program, Mt Sinai, New York, NY USA..
    Dina, Christian
    Univ Nantes, CNRS, Inst Thorax, Ctr Hosp Univ Nantes, Nantes, France..
    Thuillier, Dorothee
    Lille Inst Biol, European Genom Inst Diabet, Lille, France.;Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Yengo, Loic
    Lille Inst Biol, European Genom Inst Diabet, Lille, France.;Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Jiang, Longda
    Imperial Coll London, Dept Genom Common Dis, London, England..
    Sparso, Thomas
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Kestler, Hans A.
    Fritz Lipmann Inst, Leibniz Inst Aging, Jena, Germany.;Univ Ulm, Inst Med Syst Biol, Ulm, Germany..
    Chheda, Himanshu
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Franberg, Mattias
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Numer Anal & Comp Sci, Stockholm, Sweden..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Benediktsson, Rafn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Reykjavik, Iceland..
    Hreidarsson, Astradur B.
    Landspitali Univ Hosp, Reykjavik, Iceland..
    Kong, Augustine
    Amgen Inc, DECODE genet, Reykjavik, Iceland..
    Sigurdsson, Gunnar
    Landspitali Univ Hosp, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Kerrison, Nicola D.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Liang, Liming
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Biostatist, Boston, MA USA..
    Meitinger, Thomas
    Munich Heart Alliance, German Ctr Cardiovascular Dis, Munich, Germany.;Fritz Lipmann Inst, Leibniz Inst Aging, Jena, Germany.;Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany. Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Roden, Michael
    German Ctr Diabet Res, Neuherberg, Germany.;Heinrich Heine Univ, Fac Med, Dept Endocrinol & Diabet, Dusseldorf, Germany.;Heinrich Heine Univ Dusseldorf, Leibniz Inst Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany..
    Thorand, Barbara
    German Ctr Diabet Res, Neuherberg, Germany..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Boston Childrens Hosp, Divis Genet & Endocrinol, Boston, MA USA.;Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Fox, Caroline
    Harvard Med Sch, Divis Endocrinol, Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA USA..
    Liu, Ching-Ti
    Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Rybin, Denis
    Boston Univ Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Lyssenko, Valeriya
    Lund Univ, Univ Hosp Scania, Dept Clin Sci Malmo, Lund Univ Diabet Ctr, Lund, Sweden..
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland..
    Couper, David J.
    Univ N Carolina, Dept Biostatist, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA..
    Pankow, James S.
    Univ Minnesota, Divis Epidemiol Community Hlth, Minneapolis, MN USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Have, Christian T.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
    Jorgensen, Torben
    Capital Region Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Linneberg, Allan
    Capital Region Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshospitalet, Copenhagen, Denmark. Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-1168 Copenhagen, Denmark..
    Cornelis, Marilyn C.
    NW Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA..
    Van Dam, Rob M.
    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Hunter, David J.
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA..
    Kraft, Peter
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA..
    Sun, Qi
    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Edkins, Sarah
    Wellcome Trust Sanger Inst, Hinxton, England..
    Owen, Katharine R.
    Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.;Natl Inst Hlth Res Oxford Biomed Res Ctr, Churchill Hosp, Oxford, England..
    Perry, John R. B.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Wood, Andrew R.
    Univ Exeter Med Sch, Univ Exeter, Genet Complex Traits, Exeter, Devon, England..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Hinxton, England..
    Tajes-Fernandes, Juan
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Bonnycastle, Lori L.
    Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD USA..
    Chines, Peter S.
    Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD USA..
    Stringham, Heather M.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Cent Hosp, Dept Med & Abdominal Ctr, Endocrinol, Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Helsinki, Finland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Cent Hosp, Dept Med & Abdominal Ctr, Endocrinol, Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Helsinki, Finland..
    Sennblad, Bengt
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden..
    Muehleisen, Thomas W.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life Brain Ctr, Bonn, Germany..
    Noethen, Markus M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life Brain Ctr, Bonn, Germany..
    Pechlivanis, Sonali
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Baldassarre, Damiano
    Ist Ricovero Cura Carattere Sci, Ctr Cardiologico Monzino, Milan, Italy.;Univ Milan, Dipartimento Sci Farmacol Biomol, Milan, Italy..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Humphries, Steve E.
    UCL, Inst Cardiovascular Sci, BHF Labs, Cardiovascular Genet, London, England..
    Tremoli, Elena
    Ist Ricovero Cura Carattere Sci, Ctr Cardiologico Monzino, Milan, Italy.;Univ Milan, Dipartimento Sci Farmacol Biomol, Milan, Italy..
    Klopp, Norman
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany..
    Meyer, Julia
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Steinbach, Gerald
    Univ Ulm, Dept Clin Chem & Cent Lab, Ulm, Germany..
    Wennauer, Roman
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Peltonen, Leena
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Broad Inst & Harvard, Cambridge, MA USA..
    Tikkanen, Emmi
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland..
    Charpentier, Guillaume
    Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France..
    Eury, Elodie
    Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Lobbens, Stephane
    Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Gigante, Bruna
    Inst Environm Medi cine, Karolinska Inst, Divis Cardiovascular Epidemiol, Stockholm, Sweden..
    Leander, Karin
    Inst Environm Medi cine, Karolinska Inst, Divis Cardiovascular Epidemiol, Stockholm, Sweden..
    McLeod, Olga
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Bottinger, Erwin P.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Gottesman, Omri
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Ruderfer, Douglas
    Icahn Sch Med, Dept Psychiat, Divis Psychiat Genom, Mt Sinai, New York, NY USA..
    Blueher, Matthias
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Kovacs, Peter
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Tonjes, Anke
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Maruthur, Nisa M.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.;Johns Hopkins Bloomberg Sch Med, Dept Med, Divis Gen Internal Med, Baltimore, MD USA.;Johns Hopkins Univ, Welch Ctr Prevent, Epidemiol & Clin Res, Baltimore, MD USA..
    Scapoli, Chiara
    Univ Ferrara, Dept Life Sci & Biotechnol, Ferrara, Italy..
    Erbel, Raimund
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Joeckel, Karl-Heinz
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Moebus, Susanne
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    De Faire, Ulf
    Inst Environm Medi cine, Karolinska Inst, Divis Cardiovascular Epidemiol, Stockholm, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Stumvoll, Michael
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Deloukas, Panagiotis
    Wellcome Trust Sanger Inst, Hinxton, England.;Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Donnelly, Peter J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Frayling, Timothy M.
    Univ Exeter Med Sch, Univ Exeter, Genet Complex Traits, Exeter, Devon, England..
    Hattersley, Andrew T.
    Univ Exeter Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England..
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst tutet, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Boehm, Bernhard O.
    Univ Med Ctr Ulm, Dept Internal Med, Divis Endocrinol & Diabet, Ulm, Germany.;Nanyang Technol Univ, Imperial Coll London, Lee Kong Chian Sch Med, Singapore, Singapore..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabetes & Obes Res Inst, Los Angeles, CA USA..
    Collins, Francis S.
    Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Dasman Diabet Inst, Dasman, Kuwait.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabetes Res Grp, Jeddah, Saudi Arabia..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ So Denmark, Fac Hlth Sci, Odense, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Hinxton, England.;Addenbrookes Hosp Cambridge, Wellcome Trust MRC Inst Metab Sci, Hlth Res Cambridge Biomed Res Ctr, Cambridge, England.;Univ Cambridge Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Hlth Res Cambridge Biomed Res Ctr, Cambridge, England..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst & Harvard, Cambridge, MA USA..
    Cauchi, Stephane
    Lille Inst Biol, European Genom Inst Diabet, Lille, France..
    Froguel, Philippe
    Imperial Coll London, Dept Genom Common Dis, London, England.;Lille Inst Biol, European Genom Inst Diabet, Lille, France.;Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Loos, Ruth J. F.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA.;Icahn Sch Med, Genet Obes & Related Metab Traits Program, Mt Sinai, New York, NY USA.;Mindich Child Hlth & Dev Inst, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Balkau, Beverley
    INSERM, CESP, UMR 1018, Villejuif, France.;Univ Paris Sud, UMR 1018, Villejuif, France..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Franks, Paul W.
    Lund Univ, Malmo, Sweden.;Umea Univ, Umea, Sweden..
    Gurrea, Aurelio Barricarte
    Navarra Publ Hlth Inst, Pamplona, Spain.;Navarra Inst Hlth Res, Pamplona, Spain.;CIBER Epidemiol & Publ Hlth, Madrid, Spain..
    Palli, Domenico
    Canc Res & Prevent Inst, Florence, Italy..
    Van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Altshuler, David
    Broad Inst & Harvard, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Mol Biol, Boston, MA USA.;Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA..
    Groop, Leif C.
    Lund Univ, Univ Hosp Scania, Dept Clin Sci Malmo, Lund Univ Diabet Ctr, Lund, Sweden.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Sijbrands, Eric
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Healthy Ageing & Ctr Med Syst Biol, Netherlands Consortium, Netherlands Genom Initiat, Rotterdam, Netherlands..
    Florez, Jose C.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA USA..
    Meigs, James B.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Amgen Inc, DECODE genet, Reykjavik, Iceland.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Gen Med Divis, Boston, MA USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr, Human Genet Ctr, Houston, TX USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX USA..
    Gieger, Christian
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol II, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Genet Epidemiol, Biometry & Epidemiol, Munich, Germany..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia..
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Palmer, Colin N. A.
    Univ Dundee, Biomed Res Inst, Ninewells Hosp, Cardiovascular & Diabet Med, Dundee, Scotland..
    Hu, Frank B.
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Thorsteinsdottir, Unnur
    Amgen Inc, DECODE genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Stefansson, Kari
    Amgen Inc, DECODE genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Dupuis, Josee
    Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Morris, Andrew P.
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.;Natl Inst Hlth Res Oxford Biomed Res Ctr, Churchill Hosp, Oxford, England..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Imperial Coll London, Dept Genom Common Dis, London, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England..
    An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans2017Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, nr 11, s. 2888-2902Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.

  • 206.
    Shungin, Dmitry
    et al.
    Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Odontol, Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Unit Med, Umea, Sweden.;MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA..
    Deng, Wei Q.
    Univ Toronto, Dept Stat Sci, Toronto, ON, Canada..
    Varga, Tibor V.
    Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Univ Copenhagen, Fac Hlth & Med Sci, Translat Dis Syst Biol Grp, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark.;Lund Univ, Exercise Physiol Grp, Dept Hlth Sci, Lund, Sweden..
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia..
    Morris, Andrew P.
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Forouhi, Nita G.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Lindgren, Cecilia
    MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Hallmans, Göran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Chu, Audrey Y.
    Harvard Med Sch, Boston, MA USA..
    Justice, Anne E.
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Graff, Mariaelisa
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, DE, Germany..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.;UCL, Dept Epidemiol & Publ Hlth, London, England..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI Framingham Heart Study, Framingham, MA USA..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Ong, Ken K.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA..
    Chasman, Daniel I.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Kilpeläinen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Franks, Paul W.
    Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Unit Med, Umea, Sweden.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Univ Oxford, Radcliff Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions2017Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 6, artikkel-id e1006812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.

  • 207. Shungin, Dmitry
    et al.
    Winkler, Thomas W
    Croteau-Chonka, Damien C
    Ferreira, Teresa
    Locke, Adam E
    Mägi, Reedik
    Strawbridge, Rona J
    Pers, Tune H
    Fischer, Krista
    Justice, Anne E
    Workalemahu, Tsegaselassie
    Wu, Joseph M W
    Buchkovich, Martin L
    Heard-Costa, Nancy L
    Roman, Tamara S
    Drong, Alexander W
    Song, Ci
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Day, Felix R
    Esko, Tonu
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kutalik, Zoltán
    Luan, Jian'an
    Randall, Joshua C
    Scherag, André
    Vedantam, Sailaja
    Wood, Andrew R
    Chen, Jin
    Fehrmann, Rudolf
    Karjalainen, Juha
    Kahali, Bratati
    Liu, Ching-Ti
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Ehret, Georg B
    Feitosa, Mary F
    Goel, Anuj
    Jackson, Anne U
    Johnson, Toby
    Kleber, Marcus E
    Kristiansson, Kati
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Stančáková, Alena
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Van Vliet-Ostaptchouk, Jana V
    Yengo, Loïc
    Zhang, Weihua
    Albrecht, Eva
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Arscott, Gillian M
    Bandinelli, Stefania
    Barrett, Amy
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Blüher, Matthias
    Böhringer, Stefan
    Bonnet, Fabrice
    Böttcher, Yvonne
    Bruinenberg, Marcel
    Carba, Delia B
    Caspersen, Ida H
    Clarke, Robert
    Daw, E Warwick
    Deelen, Joris
    Deelman, Ewa
    Delgado, Graciela
    Doney, Alex S F
    Eklund, Niina
    Erdos, Michael R
    Estrada, Karol
    Eury, Elodie
    Friedrich, Nele
    Garcia, Melissa E
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grewal, Jagvir
    Groves, Christopher J
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heikkilä, Kauko
    Herzig, Karl-Heinz
    Helmer, Quinta
    Hillege, Hans L
    Holmen, Oddgeir
    Hunt, Steven C
    Isaacs, Aaron
    Ittermann, Till
    James, Alan L
    Johansson, Ingegerd
    Juliusdottir, Thorhildur
    Kalafati, Ioanna-Panagiota
    Kinnunen, Leena
    Koenig, Wolfgang
    Kooner, Ishminder K
    Kratzer, Wolfgang
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindström, Jaana
    Lobbens, Stéphane
    Lorentzon, Mattias
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Mills, Rebecca
    Moayyeri, Alireza
    Monda, Keri L
    Mooijaart, Simon P
    Mühleisen, Thomas W
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Nagaraja, Ramaiah
    Nalls, Michael A
    Narisu, Narisu
    Glorioso, Nicola
    Nolte, Ilja M
    Olden, Matthias
    Rayner, Nigel W
    Renstrom, Frida
    Ried, Janina S
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Sennblad, Bengt
    Seufferlein, Thomas
    Sitlani, Colleen M
    Vernon Smith, Albert
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tomaschitz, Andreas
    Troffa, Chiara
    van Oort, Floor V A
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Wennauer, Roman
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Zhang, Qunyuan
    Hua Zhao, Jing
    Brennan, Eoin P
    Choi, Murim
    Eriksson, Per
    Folkersen, Lasse
    Franco-Cereceda, Anders
    Gharavi, Ali G
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hivert, Marie-France
    Huang, Jinyan
    Kanoni, Stavroula
    Karpe, Fredrik
    Keildson, Sarah
    Kiryluk, Krzysztof
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McKnight, Amy J
    McPherson, Ruth
    Metspalu, Andres
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Olsson, Christian
    Perry, John R B
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Schadt, Eric E
    Scott, Robert A
    Stolk, Lisette
    Vallejo, Edgar E
    Westra, Harm-Jan
    Zondervan, Krina T
    Amouyel, Philippe
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Brown, Morris J
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chines, Peter S
    Claudi-Boehm, Simone
    Collins, Francis S
    Crawford, Dana C
    Danesh, John
    de Faire, Ulf
    de Geus, Eco J C
    Dörr, Marcus
    Erbel, Raimund
    Eriksson, Johan G
    Farrall, Martin
    Ferrannini, Ele
    Ferrières, Jean
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gieger, Christian
    Gudnason, Vilmundur
    Haiman, Christopher A
    Harris, Tamara B
    Hattersley, Andrew T
    Heliövaara, Markku
    Hicks, Andrew A
    Hingorani, Aroon D
    Hoffmann, Wolfgang
    Hofman, Albert
    Homuth, Georg
    Humphries, Steve E
    Hyppönen, Elina
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Johansen, Berit
    Jousilahti, Pekka
    Jula, Antti M
    Kaprio, Jaakko
    Kee, Frank
    Keinanen-Kiukaanniemi, Sirkka M
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Musk, Arthur W
    Möhlenkamp, Stefan
    Morris, Andrew D
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Palmer, Lyle J
    Penninx, Brenda W
    Peters, Annette
    Pramstaller, Peter P
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schwarz, Peter E H
    Shuldiner, Alan R
    Staessen, Jan A
    Steinthorsdottir, Valgerdur
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Tremblay, Angelo
    Tremoli, Elena
    Vohl, Marie-Claude
    Völker, Uwe
    Vollenweider, Peter
    Wilson, James F
    Witteman, Jacqueline C
    Adair, Linda S
    Bochud, Murielle
    Boehm, Bernhard O
    Bornstein, Stefan R
    Bouchard, Claude
    Cauchi, Stéphane
    Caulfield, Mark J
    Chambers, John C
    Chasman, Daniel I
    Cooper, Richard S
    Dedoussis, George
    Ferrucci, Luigi
    Froguel, Philippe
    Grabe, Hans-Jörgen
    Hamsten, Anders
    Hui, Jennie
    Hveem, Kristian
    Jöckel, Karl-Heinz
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    März, Winfried
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sinisalo, Juha
    Slagboom, P Eline
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Veronesi, Giovanni
    Walker, Mark
    Wareham, Nicholas J
    Watkins, Hugh
    Wichmann, H-Erich
    Abecasis, Goncalo R
    Assimes, Themistocles L
    Berndt, Sonja I
    Boehnke, Michael
    Borecki, Ingrid B
    Deloukas, Panos
    Franke, Lude
    Frayling, Timothy M
    Groop, Leif C
    Hunter, David J
    Kaplan, Robert C
    O'Connell, Jeffrey R
    Qi, Lu
    Schlessinger, David
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Willer, Cristen J
    Visscher, Peter M
    Yang, Jian
    Hirschhorn, Joel N
    Zillikens, M Carola
    McCarthy, Mark I
    Speliotes, Elizabeth K
    North, Kari E
    Fox, Caroline S
    Barroso, Inês
    Franks, Paul W
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Heid, Iris M
    Loos, Ruth J F
    Cupples, L Adrienne
    Morris, Andrew P
    Lindgren, Cecilia M
    Mohlke, Karen L
    New genetic loci link adipose and insulin biology to body fat distribution2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 187-196Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

  • 208. Soler Artigas, María
    et al.
    Wain, Louise V
    Miller, Suzanne
    Kheirallah, Abdul Kader
    Huffman, Jennifer E
    Ntalla, Ioanna
    Shrine, Nick
    Obeidat, Ma'en
    Trochet, Holly
    McArdle, Wendy L
    Alves, Alexessander Couto
    Hui, Jennie
    Zhao, Jing Hua
    Joshi, Peter K
    Teumer, Alexander
    Albrecht, Eva
    Imboden, Medea
    Rawal, Rajesh
    Lopez, Lorna M
    Marten, Jonathan
    Enroth, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Surakka, Ida
    Polasek, Ozren
    Lyytikäinen, Leo-Pekka
    Granell, Raquel
    Hysi, Pirro G
    Flexeder, Claudia
    Mahajan, Anubha
    Beilby, John
    Bossé, Yohan
    Brandsma, Corry-Anke
    Campbell, Harry
    Gieger, Christian
    Gläser, Sven
    González, Juan R
    Grallert, Harald
    Hammond, Chris J
    Harris, Sarah E
    Hartikainen, Anna-Liisa
    Heliövaara, Markku
    Henderson, John
    Hocking, Lynne
    Horikoshi, Momoko
    Hutri-Kähönen, Nina
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Kemp, John P
    Kolcic, Ivana
    Kumar, Ashish
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Melén, Erik
    Musk, Arthur W
    Navarro, Pau
    Nickle, David C
    Padmanabhan, Sandosh
    Raitakari, Olli T
    Ried, Janina S
    Ripatti, Samuli
    Schulz, Holger
    Scott, Robert A
    Sin, Don D
    Starr, John M
    Viñuela, Ana
    Völzke, Henry
    Wild, Sarah H
    Wright, Alan F
    Zemunik, Tatijana
    Jarvis, Deborah L
    Spector, Tim D
    Evans, David M
    Lehtimäki, Terho
    Vitart, Veronique
    Kähönen, Mika
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rudan, Igor
    Deary, Ian J
    Karrasch, Stefan
    Probst-Hensch, Nicole M
    Heinrich, Joachim
    Stubbe, Beate
    Wilson, James F
    Wareham, Nicholas J
    James, Alan L
    Morris, Andrew P
    Jarvelin, Marjo-Riitta
    Hayward, Caroline
    Sayers, Ian
    Strachan, David P
    Hall, Ian P
    Tobin, Martin D
    Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation2015Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikkel-id 8658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

  • 209.
    Song, Ci
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Chang, Z
    Magnusson, P K E
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Pedersen, N L
    Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors2014Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 6, s. 631-639Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD).

    DESIGN: The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene-environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors.

    SUBJECTS: In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded.

    RESULTS: Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women.

    CONCLUSIONS: The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene-environment interactions will be important for a full understanding of the aetiology of CHD.

  • 210. Song, Ci
    et al.
    Pedersen, Nancy L.
    Reynolds, Chandra A.
    Sabater-Lleal, Maria
    Kanoni, Stavroula
    Willenborg, Christina
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Watkins, Hugh
    Hamsten, Anders
    Prince, Jonathan A.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Genetic Variants from Lipid-Related Pathways and Risk for Incident Myocardial Infarction2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 3, s. e60454-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Circulating lipids levels, as well as several familial lipid metabolism disorders, are strongly associated with initiation and progression of atherosclerosis and incidence of myocardial infarction (MI). Objectives: We hypothesized that genetic variants associated with circulating lipid levels would also be associated with MI incidence, and have tested this in three independent samples. Setting and Subjects: Using age- and sex-adjusted additive genetic models, we analyzed 554 single nucleotide polymorphisms (SNPs) in 41 candidate gene regions proposed to be involved in lipid-related pathways potentially predisposing to incidence of MI in 2,602 participants of the Swedish Twin Register (STR; 57% women). All associations with nominal P<0.01 were further investigated in the Uppsala Longitudinal Study of Adult Men (ULSAM; N = 1,142). Results: In the present study, we report associations of lipid-related SNPs with incident MI in two community-based longitudinal studies with in silico replication in a meta-analysis of genome-wide association studies. Overall, there were 9 SNPs in STR with nominal P-value <0.01 that were successfully genotyped in ULSAM. rs4149313 located in ABCA1 was associated with MI incidence in both longitudinal study samples with nominal significance (hazard ratio, 1.36 and 1.40; P-value, 0.004 and 0.015 in STR and ULSAM, respectively). In silico replication supported the association of rs4149313 with coronary artery disease in an independent meta-analysis including 173,975 individuals of European descent from the CARDIoGRAMplusC4D consortium (odds ratio, 1.03; P-value, 0.048). Conclusions: rs4149313 is one of the few amino acid changing variants in ABCA1 known to associate with reduced cholesterol efflux. Our results are suggestive of a weak association between this variant and the development of atherosclerosis and MI.

  • 211.
    Spracklen, Cassandra N.
    et al.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Eastern Mediterranean Univ, Fac Arts & Sci, Dept Biol Sci, Gazimagusa, Cyprus;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark;Tech Univ Denmark, DTU Hlth Technol, DK-2800 Lyngby, Denmark.
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England;Univ Westminster, Sch Life Sci, Res Ctr Optimal Hlth, London, England.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Fine, Rebecca S.
    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Kutalik, Zoltan
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England;Univ Lausanne, Univ Ctr Primary Care & Publ Hlth, CH-1010 Lausanne, Switzerland;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Sch Med, Nashville, TN 37203 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
    Wittemans, Laura B. L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Adair, Linda S.
    Univ North Carolina Chapel Hill, Carolina Populat Ctr, Chapel Hill, NC 27516 USA.
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92093 USA.
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    Auer, Paul L.
    Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA;Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Blueher, Matthias
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Borja, Judith B.
    Off Populat Studies Fdn Inc, Cebu, Philippines;Univ San Carlos, Dept Nutr & Dietet, Cebu, Philippines.
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Broer, Linda
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Chirstofidou, Paraskevi
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Demirkan, Ayse
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Garcia, Melissa E.
    NHLBI, Bldg 10, Bethesda, MD 20892 USA.
    Graff, Mariaelisa
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA;Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
    Grallert, Harald
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Haesser, Jeffrey
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Highland, Heather M.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Hong, Jaeyoung
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA;Stanford Univ, Stanford Cardiovasc Inst, Palo Alto, CA 94304 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jackson, Rebecca
    Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33522, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere 33522, Finland.
    Kizer, Jorge R.
    Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
    Kovacs, Peter
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70029, Kys, Finland;Kuopio Univ Hosp, Kuopio 70029, Kys, Finland.
    Lange, Leslie A.
    Univ Colorado, Dept Med, Div Biomed Informat & Personalized Med, Denver, CO 80045 USA.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33522, Finland.
    Li, Jin
    Stanford Univ, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA.
    Li-Gao, Ruifang
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33522, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33521, Finland.
    MacGregor, Stuart
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
    Mackey, David A.
    Univ Western Australia, Fac Hlth & Med Sci, Perth, WA 6009, Australia;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England.
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7FZ, England.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Medina-Gomez, Carolina
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Broad Inst, Program Populat & Med Genet, Cambridge, MA 02114 USA.
    Molnos, Sophie
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2334 ZA Leiden, Netherlands.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands.
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD 20812 USA.
    Nedeljkovic, Ivana
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    North, Kari E.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Pennell, Craig E.
    Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW 2305, Australia.
    Pradhan, Aruna D.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Raitakari, Olli T.
    Univ Turku, Ctr Populat Hlth Res, Turku, Finland;Turku Univ Hosp, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
    Raulerson, Chelsea K.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Ripatti, Samuli
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Univ Helsinki, Publ Hlth, FIN-00014 Helsinki, Finland;Inst Mol Med Finland, Helsinki 00014, Finland.
    Roberston, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    Sandoval-Zarate, America A.
    Inst Mol Med Finland, Helsinki 00014, Finland.
    Sitlani, Colleen M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.
    Stumvoll, Michael
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Thuesen, Betina
    Capital Reg, Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Dis Prevent, DK-2400 Copenhagen, Denmark.
    Toenjes, Anke
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Venturini, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Wang, Carol A.
    Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW 2305, Australia.
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Willems, Sara M.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    van Dijk, Ko Willems
    Leiden Univ, Med Ctr, Div Endocrinol, Dept Internal Med, NL-2333 ZA Leiden, Netherlands;Einthoven Lab Expt Vasc Med, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Young, Kristin L.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England.
    Kilpelainen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Univ Oxford, Nuffield Dept Med, Big Data Inst, Oxford OX3 7LF, England.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology2019Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 105, nr 1, s. 15-28Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 x 10(-7)). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r(2) > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

  • 212.
    Stenemo, M. Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Proteomic profiling and the risk of heart failure2015Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, s. 141-141Artikkel i tidsskrift (Annet vitenskapelig)
  • 213.
    Stenemo, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA ; Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA ; Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA ; Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi. George Inst Global Hlth, Sydney, NSW, Australia.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Broeckling, Corey
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA ; Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA.
    Svensson, Per
    Karolinska Inst, Dept Clin Sci & Educ, Dept Cardiol, Sodersjukhuset, Stockholm, Sweden.
    Magnusson, Patrik
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA ; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA ; Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden ; Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population2019Inngår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, nr 4, s. 764-773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction.

    Methods: Mass spectrometry-based metabolomic profiling was performed in plasma or serum samples from three community-based cohorts without heart failure at baseline (total n=3,924; 341 incident heart failure events, median follow-up ranging from 4.6 to 13.9 years). Cox proportional hazards models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n=920) and Uppsala Longitudinal Study of Adult Men (ULSAM, n=1,121). Replication was undertaken in the independent cohort TwinGene (n=1,797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low-density lipoprotein- and high-density lipoprotein-cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow-up).

    Results: Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age- and sex-adjusted models in the discovery and replication sample. The hazard ratio (HR) for urobilin in the replication cohort was estimated to 1.29 per SD unit, 95% confidence interval (CI) 1.03-1.63) and for sphingomyelin (30:1) to 0.72 (95% CI 0.58-0.89). Results remained similar after further adjustment for established heart failure risk factors in meta-analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β= -0.70 (95% CI -1.03-(-0.38)). No improvement in risk prediction was observed when adding the two top metabolites (C-index 0.787 (95% CI 0.752-0.823)) or nine Lasso-selected metabolites (0.790 (95% CI 0.754-0.826)) to a modified Atherosclerosis Risk in Communities (ARIC) heart failure risk score model (0.780 (95% CI 0.745-0.816)).

    Conclusions: Our metabolomics study identified associations of circulating levels of the heme breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

  • 214.
    Stenemo, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ärnlöv, Johan
    Dalarna University, School of Health and Social Studies, Falun; Karolinska Institutet, Care Science and Society, Department of Neurobiology, Division of Family Medicine and Primary Care .
    Circulating proteins as predictors of incident heart failure in the elderly2018Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims

    To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

    Methods and results

    Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

    Conclusion

    Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

  • 215. Stolk, Lisette
    et al.
    Perry, John R B
    Chasman, Daniel I
    He, Chunyan
    Mangino, Massimo
    Sulem, Patrick
    Barbalic, Maja
    Broer, Linda
    Byrne, Enda M
    Ernst, Florian
    Esko, Tõnu
    Franceschini, Nora
    Gudbjartsson, Daniel F
    Hottenga, Jouke-Jan
    Kraft, Peter
    McArdle, Patrick F
    Porcu, Eleonora
    Shin, So-Youn
    Smith, Albert V
    van Wingerden, Sophie
    Zhai, Guangju
    Zhuang, Wei V
    Albrecht, Eva
    Alizadeh, Behrooz Z
    Aspelund, Thor
    Bandinelli, Stefania
    Lauc, Lovorka Barac
    Beckmann, Jacques S
    Boban, Mladen
    Boerwinkle, Eric
    Broekmans, Frank J
    Burri, Andrea
    Campbell, Harry
    Chanock, Stephen J
    Chen, Constance
    Cornelis, Marilyn C
    Corre, Tanguy
    Coviello, Andrea D
    d'Adamo, Pio
    Davies, Gail
    de Faire, Ulf
    de Geus, Eco J C
    Deary, Ian J
    Dedoussis, George V Z
    Deloukas, Panagiotis
    Ebrahim, Shah
    Eiriksdottir, Gudny
    Emilsson, Valur
    Eriksson, Johan G
    Fauser, Bart C J M
    Ferreli, Liana
    Ferrucci, Luigi
    Fischer, Krista
    Folsom, Aaron R
    Garcia, Melissa E
    Gasparini, Paolo
    Gieger, Christian
    Glazer, Nicole
    Grobbee, Diederick E
    Hall, Per
    Haller, Toomas
    Hankinson, Susan E
    Hass, Merli
    Hayward, Caroline
    Heath, Andrew C
    Hofman, Albert
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Janssens, A Cecile J W
    Johnson, Andrew D
    Karasik, David
    Kardia, Sharon L R
    Keyzer, Jules
    Kiel, Douglas P
    Kolcic, Ivana
    Kutalik, Zoltán
    Lahti, Jari
    Lai, Sandra
    Laisk, Triin
    Laven, Joop S E
    Lawlor, Debbie A
    Liu, Jianjun
    Lopez, Lorna M
    Louwers, Yvonne V
    Magnusson, Patrik K E
    Marongiu, Mara
    Martin, Nicholas G
    Klaric, Irena Martinovic
    Masciullo, Corrado
    McKnight, Barbara
    Medland, Sarah E
    Melzer, David
    Mooser, Vincent
    Navarro, Pau
    Newman, Anne B
    Nyholt, Dale R
    Onland-Moret, N Charlotte
    Palotie, Aarno
    Paré, Guillaume
    Parker, Alex N
    Pedersen, Nancy L
    Peeters, Petra H M
    Pistis, Giorgio
    Plump, Andrew S
    Polasek, Ozren
    Pop, Victor J M
    Psaty, Bruce M
    Räikkönen, Katri
    Rehnberg, Emil
    Rotter, Jerome I
    Rudan, Igor
    Sala, Cinzia
    Salumets, Andres
    Scuteri, Angelo
    Singleton, Andrew
    Smith, Jennifer A
    Snieder, Harold
    Soranzo, Nicole
    Stacey, Simon N
    Starr, John M
    Stathopoulou, Maria G
    Stirrups, Kathleen
    Stolk, Ronald P
    Styrkarsdottir, Unnur
    Sun, Yan V
    Tenesa, Albert
    Thorand, Barbara
    Toniolo, Daniela
    Tryggvadottir, Laufey
    Tsui, Kim
    Ulivi, Sheila
    van Dam, Rob M
    van der Schouw, Yvonne T
    van Gils, Carla H
    van Nierop, Peter
    Vink, Jacqueline M
    Visscher, Peter M
    Voorhuis, Marlies
    Waeber, Gérard
    Wallaschofski, Henri
    Wichmann, H Erich
    Widen, Elisabeth
    Wijnands-van Gent, Colette J M
    Willemsen, Gonneke
    Wilson, James F
    Wolffenbuttel, Bruce H R
    Wright, Alan F
    Yerges-Armstrong, Laura M
    Zemunik, Tatijana
    Zgaga, Lina
    Zillikens, M Carola
    Zygmunt, Marek
    Study, The Lifelines Cohort
    Arnold, Alice M
    Boomsma, Dorret I
    Buring, Julie E
    Crisponi, Laura
    Demerath, Ellen W
    Gudnason, Vilmundur
    Harris, Tamara B
    Hu, Frank B
    Hunter, David J
    Launer, Lenore J
    Metspalu, Andres
    Montgomery, Grant W
    Oostra, Ben A
    Ridker, Paul M
    Sanna, Serena
    Schlessinger, David
    Spector, Tim D
    Stefansson, Kari
    Streeten, Elizabeth A
    Thorsteinsdottir, Unnur
    Uda, Manuela
    Uitterlinden, André G
    van Duijn, Cornelia M
    Völzke, Henry
    Murray, Anna
    Murabito, Joanne M
    Visser, Jenny A
    Lunetta, Kathryn L
    Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 3, s. 260-268Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

  • 216.
    Sundelöf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Irizarry, Michael C
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Rönnemaa, Elina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gunnarsson, Malin Degerman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hyman, Bradley T
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men: A Prospective, Population-Based Cohort Study2008Inngår i: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 65, nr 2, s. 256-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Beta amyloid (Abeta) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma. OBJECTIVE: To examine plasma levels of Abeta peptides Abeta(40) and Abeta(42) as predictors of incident AD and other types of dementia. DESIGN: Prospective, population-based cohort study. SETTING: The Uppsala Longitudinal Study of Adult Men. PARTICIPANTS: Plasma Abeta(40) and Abeta(42) levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review. MAIN OUTCOME MEASURES: Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma Abeta(40) and Abeta(42). RESULTS: From the age of 77 years at baseline, 46 individuals developed AD at follow-up (median, 5.3 years). A low plasma Abeta(40) level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest Abeta(40) tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 individuals developed AD. Plasma Abeta(40) and Abeta(42) levels measured at age 70 years were not significantly associated with incident AD. CONCLUSIONS: Low plasma Abeta(40) levels predicted incident AD in elderly men independently of potential confounders. Plasma Abeta(42) levels were not significantly associated with AD incidence. The clinical value of Abeta measurement in plasma remains to be established in future studies.

  • 217.
    Sundelöf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, J.
    Ingelsson, E.
    Sundström, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Irizarry, M. C.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Rönnemaa, Elina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Degerman-Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hyman, B. T.
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Serum cystatin C and the risk of Alzheimer disease in elderly men2008Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, nr 14, s. 1072-1079Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.

  • 218.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cardiac troponin-I and risk of heart failure: a community-based cohort study2009Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, nr 7, s. 773-781Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: We examined if circulating levels of cardiac troponin-I (cTnI) predict subsequent heart failure in the community. METHODS AND RESULTS: Using Cox proportional hazards models, we examined the risk of a first hospitalization for heart failure during a maximum of 11.4 years in a community-based sample of 1089 70-year-old men without heart failure, valvular disease, or electrocardiographic left ventricular hypertrophy. Adjusting for smoking, systolic blood pressure, antihypertensive medication use, diabetes, body mass index, serum cholesterol, and myocardial infarction before baseline or during follow-up, 0.01 microg/L higher cTnI conferred a hazard ratio (HR) of 1.26 (95% confidence interval 1.15-1.38) for subsequent heart failure. Persons with cTnI > or =0.03 microg/L had an HR of 5.25 (2.00-13.77) compared with persons with cTnI <0.01 microg/L. Adjusting additionally for serum NTproBNP attenuated the estimates somewhat [HR 1.22 (1.11-1.34) per 0.01 microg/L of cTnI]. Excluding persons with myocardial infarction before baseline and censoring at time of myocardial infarction during follow-up, 0.01 microg/L higher cTnI was associated with a multivariable-adjusted HR of 1.31 (1.16-1.47) for heart failure. CONCLUSION: In a community-based sample, a direct measure of cardiomyocyte damage, cTnI, indicated a substantially increased risk of heart failure, accounting for other risk factors. Studies investigating the clinical utility of measuring cTnI in asymptomatic individuals are warranted.

  • 219.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vallhagen, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Risk associated with the metabolic syndrome versus the sum of its individual components2006Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, nr 7, s. 1673-1674Artikkel i tidsskrift (Fagfellevurdert)
  • 220. Surakka, Ida
    et al.
    Horikoshi, Momoko
    Magi, Reedik
    Sarin, Antti-Pekka
    Mahajan, Anubha
    Lagou, Vasiliki
    Marullo, Letizia
    Ferreira, Teresa
    Miraglio, Benjamin
    Timonen, Sanna
    Kettunen, Johannes
    Pirinen, Matti
    Karjalainen, Julia
    Thorleifsson, Gudmar
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hottenga, Jouke-Jan
    Isaacs, Aaron
    Ladenvall, Claes
    Beekman, Marian
    Esko, Tonu
    Ried, Janina S.
    Nelson, Christopher P.
    Willenborg, Christina
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Westra, Harm-Jan
    Blades, Matthew
    de Craen, Anton J. M.
    de Geus, Eco J.
    Deelen, Joris
    Grallert, Harald
    Hamsten, Anders
    Havulinna, Aki S.
    Hengstenberg, Christian
    Houwing-Duistermaat, Jeanine J.
    Hypponen, Elina
    Karssen, Lennart C.
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Magnusson, Patrik K. E.
    Mihailov, Evelin
    Muller-Nurasyid, Martina
    Mpindi, John-Patrick
    Pedersen, Nancy L.
    Penninx, Brenda W. J. H.
    Perola, Markus
    Pers, Tune H.
    Peters, Annette
    Rung, Johan
    Smit, Johannes H.
    Steinthorsdottir, Valgerdur
    Tobin, Martin D.
    Tsernikova, Natalia
    van Leeuwen, Elisabeth M.
    Viikari, Jorma S.
    Willems, Sara M.
    Willemsen, Gonneke
    Schunkert, Heribert
    Erdmann, Jeanette
    Samani, Nilesh J.
    Kaprio, Jaakko
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Gieger, Christian
    Metspalu, Andres
    Slagboom, P. Eline
    Groop, Leif
    van Duijn, Cornelia M.
    Eriksson, Johan G.
    Jula, Antti
    Salomaa, Veikko
    Boomsma, Dorret I.
    Power, Christine
    Raitakari, Olli T.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jarvelin, Marjo-Riitta
    Thorsteinsdottir, Unnur
    Franke, Lude
    Ikonen, Elina
    Kallioniemi, Olli
    Pietiainen, Vilja
    Lindgren, Cecilia M.
    Stefansson, Kari
    Palotie, Aarno
    McCarthy, Mark I.
    Morris, Andrew P.
    Prokopenko, Inga
    Ripatti, Samuli
    The impact of low-frequency and rare variants on lipid levels2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 6, s. 589-597Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.

  • 221. Swaminathan, Bhairavi
    et al.
    Thorleifsson, Guomar
    Joud, Magnus
    Ali, Mina
    Johnsson, Ellinor
    Ajore, Ram
    Sulem, Patrick
    Halvarsson, Britt-Marie
    Eyjolfsson, Guomundur
    Haraldsdottir, Vilhelmina
    Hultman, Christina
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Kristinsson, Sigurour Y.
    Kahler, Anna K.
    Lenhoff, Stig
    Masson, Gisli
    Mellqvist, Ulf-Henrik
    Mansson, Robert
    Nelander, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Olafsson, Isleifur
    Siguroardottir, Olof
    Steingrimsdottir, Hlif
    Vangsted, Annette
    Vogel, Ulla
    Waage, Anders
    Nahi, Hareth
    Gudbjartsson, Daniel F.
    Rafnar, Thorunn
    Turesson, Ingemar
    Gullberg, Urban
    Stefansson, Kari
    Hansson, Markus
    Thorsteinsdottir, Unnur
    Nilsson, Bjorn
    Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma2015Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikkel-id 7213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR) = 1.25; P = 9.6 x 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P = 8.6 x 10(-9) and P = 6.4 x 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR = 1.30; P = 0.0024).

  • 222. Tang, Wenbo
    et al.
    Kowgier, Matthew
    Loth, Daan W.
    Artigas, Maria Soler
    Joubert, Bonnie R.
    Hodge, Emily
    Gharib, Sina A.
    Smith, Albert V.
    Ruczinski, Ingo
    Gudnason, Vilmundur
    Mathias, Rasika A.
    Harris, Tamara B.
    Hansel, Nadia N.
    Launer, Lenore J.
    Barnes, Kathleen C.
    Hansen, Joyanna G.
    Albrecht, Eva
    Aldrich, Melinda C.
    Allerhand, Michael
    Barr, R. Graham
    Brusselle, Guy G.
    Couper, David J.
    Curjuric, Ivan
    Davies, Gail
    Deary, Ian J.
    Dupuis, Josee
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Foy, Millennia
    Franceschini, Nora
    Gao, Wei
    Glaeser, Sven
    Gu, Xiangjun
    Hancock, Dana B.
    Heinrich, Joachim
    Hofman, Albert
    Imboden, Medea
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    James, Alan
    Karrasch, Stefan
    Koch, Beate
    Kritchevsky, Stephen B.
    Kumar, Ashish
    Lahousse, Lies
    Li, Guo
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia
    Liu, Yongmei
    Lohman, Kurt
    Lumley, Thomas
    McArdle, Wendy L.
    Meibohm, Bernd
    Morris, Andrew P.
    Morrison, Alanna C.
    Musk, Bill
    North, Kari E.
    Palmer, Lyle J.
    Probst-Hensch, Nicole M.
    Psaty, Bruce M.
    Rivadeneira, Fernando
    Rotter, Jerome I.
    Schulz, Holger
    Smith, Lewis J.
    Sood, Akshay
    Starr, John M.
    Strachan, David P.
    Teumer, Alexander
    Uitterlinden, Andre G.
    Voelzke, Henry
    Voorman, Arend
    Wain, Louise V.
    Wells, Martin T.
    Wilk, Jemma B.
    Williams, O. Dale
    Heckbert, Susan R.
    Stricker, Bruno H.
    London, Stephanie J.
    Fornage, Myriam
    Tobin, Martin D.
    O'Connor, George T.
    Hall, Ian P.
    Cassano, Patricia A.
    Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, s. e100776-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 x 10(-7)). In addition, meta-analysis using the five cohorts with >= 3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 x 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  • 223.
    Teumer, Alexander
    et al.
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Li, Yong
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany.
    Ghasemi, Sahar
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Prins, Bram P.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Wuttke, Matthias
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Fac Med & Med Ctr, Dept Med, Renal Div, Freiburg, Germany.
    Hermle, Tobias
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Welch Ctr Prevent, Epidemiol & Clin Res, Baltimore, MD USA.
    Giri, Ayush
    Vanderbilt Univ, Med Ctr,Div Quantitat Sci, Dept Obstet & Gynecol,Vanderbilt Genet Inst, Inst Med & Publ Hlth,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA;Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Biomed Lab Res & Dev, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Sieber, Karsten B.
    GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA.
    Qiu, Chengxiang
    Univ Penn, Dept Med, Dept Genet, Renal Elect & Hypertens,Div Perelman Sch Med, Philadelphia, PA 19104 USA.
    Kirsten, Holger
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Tin, Adrienne
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Welch Ctr Prevent, Epidemiol & Clin Res, Baltimore, MD USA.
    Chu, Audrey Y.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Bansal, Nisha
    Univ Washington, Div Nephrol, Seattle, WA 98195 USA;Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Wang, Lihua
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Chai, Jin-Fang
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Cocca, Massimiliano
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Fuchsberger, Christian
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Gorski, Mathias
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Hoppmann, Anselm
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany.
    Horn, Katrin
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Li, Man
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Noce, Damia
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Nutile, Teresa
    CNR, Inst Genet & Biophys Adriano Buzzati Traveso, Naples, Italy.
    Sedaghat, Sanaz
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Sveinbjornsson, Gardar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Tayo, Bamidele O.
    Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA.
    Van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Xu, Yizhe
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Yu, Zhi
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
    Gerstner, Lea
    Univ Freiburg, Fac Med & Med Ctr, Dept Med, Renal Div, Freiburg, Germany.
    Arnlov, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Bakker, Stephan J. L.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands.
    Baptista, Daniela
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Biggs, Mary L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Carroll, Robert J.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Chee, Miao-Li
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Chee, Miao-Ling
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Chen, Mengmeng
    Univ Freiburg, Fac Med & Med Ctr, Dept Med, Renal Div, Freiburg, Germany.
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Singapore, Singapore;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Corre, Tanguy
    Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland;Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Danesh, John
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    de Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands.
    De Grandi, Alessandro
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    de Vries, Aiko P. J.
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Nephrol, Leiden, Netherlands.
    Degenhardt, Frauke
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
    Dittrich, Katalin
    Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Divers, Jasmin
    Wake Forest Sch Med, Dept Biostat & Data Sci, Winston Salem, NC USA.
    Eckardt, Kai-Uwe
    Charite, Intens Care Med, Berlin, Germany;Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Nephrol & Hypertens, Erlangen, Germany.
    Ehret, Georg
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Endlich, Karlhans
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Dept Anat & Cell Biol, Greifswald, Germany.
    Felix, Janine F.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Bern, ISPM, Bern, Switzerland.
    Franke, Andre
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
    Freedman, Barry I.
    Wake Forest Sch Med, Internal Med Sect Nephrol, Winston Salem, NC USA.
    Freitag-Wolf, Sandra
    Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany.
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gogele, Martin
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Grundner-Culemann, Franziska
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany.
    Gudbjartsson, Daniel F.
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
    Hamet, Pavel
    CHUM, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada;Medpharmgene, Montreal, PQ, Canada.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
    Hicks, Andrew A.
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Holm, Hilma
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Foo, Valencia Hui Xian
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Hwang, Shih-Jen
    NHLBIs Framingham Heart Study, Framingham, MA USA;NHLBI, Ctr Populat Studies, Framingham, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jaddoe, Vincent W. V.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Jakobsdottir, Johanna
    Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland;Univ Iceland, Ctr Publ Hlth Sci, Sturlugata 8, IS-101 Reykjavik, Iceland.
    Josyula, Navya Shilpa
    Geisinger Res Biomed & Translat Informat Inst, Rockville, MD USA.
    Jung, Bettina
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere, Finland.
    Khor, Chiea-Chuen
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
    Kiess, Wieland
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Koenig, Wolfgang
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Univ Ulm, Inst Epidemiol & Biostat, Ulm, Germany.
    Koerner, Antje
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Kovacs, Peter
    Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Leipzig, Germany.
    Kramer, Holly
    Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA;Loyola Univ Chicago, Div Nephrol & Hypertens, Chicago, IL USA.
    Kraemer, Bernhard K.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol 5, Hypertensiol,Rheumatol,Endocrinol,Diabetol, Mannheim, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lange, Leslie A.
    Univ Colorado Denver, Sch Med, Div Biomed Informat & Personalized Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Dept Biostat & Data Sci, Winston Salem, NC USA.
    Lee, Jeannette Jen-Mai
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol, Kiel, Germany;Univ Kiel, Biobank Popgen, Kiel, Germany.
    Lim, Su-Chi
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Khoo Teck Puat Hosp, Diabetes Ctr, Singapore, Singapore.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Oxford, England;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Liu, Jianjun
    Natl Univ Hlth Syst, Singapore, Singapore;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Maranville, Joseph C.
    Merck & Co Inc, MRL, Kenilworth, NJ USA;Celgene Inc, Cambridge, MA USA.
    Mascalzoni, Deborah
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    McMullen, Barbara
    Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Independent Res Grp Clin Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, UNIKA T Augsburg, Chair Epidemiol, Augsburg, Germany.
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Miliku, Kozeta
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany;LMU, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany;Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, Munich, Germany.
    Mychaleckyj, Josyf C.
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
    Nikus, Kjell
    Tampere Univ Hosp, Heart Ctr, Dept Cardiol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Cardiol, Tampere, Finland.
    Ning, Boting
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    Connell, Jeffrey O'
    Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
    Olafsson, Isleifur
    Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland.
    Palmer, Nicholette D.
    Wake Forest Sch Med, Biochem, Winston Salem, NC USA.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Podgornaia, Anna I.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Ponte, Belen
    Geneva Univ Hosp, Serv Nephrol, Geneva, Switzerland.
    Poulain, Tanja
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Pramstaller, Peter P.
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Rabelink, Ton J.
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Nephrol, Leiden, Netherlands;Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Res, Leiden, Netherlands.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Reilly, Dermot F.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany.
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rivadeneira, Fernando
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Runz, Heiko
    Merck & Co Inc, MRL, Kenilworth, NJ USA;Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
    Ryan, Kathleen A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
    Sabanayagam, Charumathi
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
    Saum, Kai-Uwe
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Schoettker, Ben
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Shaffer, Christian M.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Shi, Yuan
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
    Smith, Albert V.
    Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany;LMU, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany.
    Stumvoll, Michael
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Sun, Benjamin B.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Szymczak, Silke
    Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany.
    Tai, E-Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore;Duke NUS Med Sch, Singapore, Singapore.
    Tan, Nicholas Y. Q.
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teren, Andrej
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Heart Ctr Leipzig, Leipzig, Germany.
    Tham, Yih-Chung
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany.
    Thio, Chris H. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Thomsen, Hauke
    German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Tonjes, Anke
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Tremblay, Johanne
    CHUM, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada;CRCHUM, Montreal, PQ, Canada.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Vogelezang, Suzanne
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Waldenberger, Melanie
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Wang, Chaolong
    Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Wuhan, Hubei, Peoples R China.
    Wilson, Otis D.
    Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN USA.
    Wong, Charlene
    Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Wong, Tien-Yin
    Natl Univ Hlth Syst, Singapore, Singapore;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Yasuda, Masayuki
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Sendai, Miyagi, Japan.
    Akilesh, Shreeram
    Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA;Univ Washington, Med Ctr, Anat Pathol, Seattle, WA 98195 USA.
    Bochud, Murielle
    Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland.
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Kliniken Sudostbayern, Dept Nephrol Diabetol & Rheumatol, Traunstein, Germany.
    Devuyst, Olivier
    Univ Zurich, Inst Physiol, Zurich, Switzerland.
    Edwards, Todd L.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol,Vanderbilt Genet Inst, Nashville, TN USA;Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Ho, Kevin
    Geisinger, KHRI, Danville, PA USA;Geisinger, Dept Nephrol, Danville, PA USA.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Parsa, Afshin
    NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA;Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Pendergrass, Sarah A.
    Geisinger Res, Biomed & Translat Informat Inst, Danville, PA USA.
    Psaty, Bruce M.
    Univ Washington, Dept Hlth Serv, Dept Epidemiol, Cardiovasc Hlth Res Unit,Dept Med, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Med, Torrance, CA 90509 USA.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Phys & Biophys, Jackson, MS 39216 USA.
    Susztak, Katalin
    Univ Penn, Dept Med, Dept Genet, Renal Elect & Hypertens,Div Perelman Sch Med, Philadelphia, PA 19104 USA.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Res Unit Do, Cambridge, England.
    Hung, Adriana M.
    Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN USA;Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Pattaro, Cristian
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Koettgen, Anna
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria2019Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, artikkel-id 4130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n =192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

  • 224.
    Tikkanen, Emmi
    et al.
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, 300 Pasteur Dr, Stanford, CA 94305 USA.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Knowles, Joshua W.
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, 300 Pasteur Dr, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA.
    Perez, Marco
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA.
    Burgess, Stephen
    Univ Cambridge, MRC Biostat Unit, Cambridge Inst Publ Hlth, Forv Site,Robinson Way,Cambridge Biomed Campus, Cambridge CB2 0SR, England;Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, 300 Pasteur Dr, Stanford, CA 94305 USA; Stanford Univ, Stanford Diabet Res Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA.
    Body composition and atrial fibrillation: a Mendelian randomization study2019Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, nr 16, s. 1277-1282Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims

    Increases in fat-free mass and fat mass have been associated with higher risk of atrial fibrillation (AF) in observational studies. It is not known whether these associations reflect independent causal processes. Our aim was to evaluate independent causal roles of fat-free mass and fat mass on AF.

    Methods and results

    We conducted a large observational study to estimate the associations between fat-free mass and fat mass on incident AF in the UK Biobank (N = 487 404, N events = 10 365). Genome-wide association analysis was performed to obtain genetic instruments for Mendelian randomization (MR). We evaluated the causal effects of fat-free mass and fat mass on AF with two-sample method by using genetic associations from AFGen consortium as outcome. Finally, we evaluated independent causal effects of fat-free mass and fat mass with multivariate MR. Both fat-free mass and fat mass had observational associations with incident AF [hazard ratio (HR) = 1.77, 95% confidence interval (CI) 1.72-1.83; HR = 1.40, 95% CI 1.37-1.43 per standard deviation increase in fat-free and fat mass, respectively]. The causal effects using the inverse-variance weighted method were 1.55 (95% CI 1.38-1.75) for fat-free mass and 1.30 (95% CI 1.17-1.45) for fat mass. Weighted median, Egger regression, and penalized methods showed similar estimates. The multivariate MR analysis suggested that the causal effects of fat-free and fat mass were independent of each other (causal risk ratios: 1.37, 95% CI 1.06-1.75; 1.28, 95% CI 1.03-1.58).

    Conclusion

    Genetically programmed increases in fat-free mass and fat mass independently cause an increased risk of AF.

  • 225.
    Tin, Adrienne
    et al.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA;Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Kuhns, Victoria L. Halperin
    Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
    Li, Yong
    Univ Freiburg, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Fac Med, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Wuttke, Matthias
    Univ Freiburg, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Fac Med, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Kirsten, Holger
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Sieber, Karsten B.
    GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA.
    Qiu, Chengxiang
    Univ Penn, Dept Med & Genet, Philadelphia, PA 19104 USA.
    Gorski, Mathias
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Yu, Zhi
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
    Giri, Ayush
    Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth,Div Quantitat Sci,Dept Obste, Vanderbilt Genet Inst,Vanderbilt Epidemiol Ctr, Nashville, TN USA;Vanderbilt Univ, Biomed Lab Res & Dev, Tennessee Valley Healthcare Syst 626, Nashville, TN USA.
    Sveinbjornsson, Gardar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Li, Man
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Chu, Audrey Y.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Hoppmann, Anselm
    Univ Freiburg, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Fac Med, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    O'Connor, Luke J.
    Harvard TH Chan Sch Publ Hlth, Epidemiol, Boston, MA USA.
    Prins, Bram
    Univ Cambridge, Strangeways Res Lab, Cambridge, England.
    Nutile, Teresa
    CNR, Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy.
    Noce, Damia
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Akiyama, Masato
    RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan;Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka, Japan.
    Cocca, Massimiliano
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Ghasemi, Sahar
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    van Der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Horn, Katrin
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Xu, Yizhe
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Fuchsberger, Christian
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Sedaghat, Sanaz
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
    Afaq, Saima
    Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Khyber Med Univ, Inst Publ Hlth & Social Sci, Peshawar, Pakistan.
    Amin, Najaf
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Bakker, Stephan J. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
    Bansal, Nisha
    Univ Washington, Div Nephrol, Seattle, WA 98195 USA;Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
    Baptista, Daniela
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland;Univ Cape Town, Dept Integrat Biomed Sci, Cape Town, South Africa.
    Biggs, Mary L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Biino, Ginevra
    Natl Res Council Italy, Inst Mol Genet, Pavia, Italy.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Hasso Plattner Inst Digital Hlth Mt Sinai, New York, NY 10029 USA.
    Boutin, Thibaud S.
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Brumat, Marco
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Campana, Eric
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Campbell, Archie
    Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Campbell, Harry
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Carroll, Robert J.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Catamo, Eulalia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Chambers, John C.
    Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore;Ealing Gen Hosp, Dept Cardiol, London, England;Imperial Coll Healthcare NHS Trust, Imperial Coll London, London, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England.
    Ciullo, Marina
    CNR, Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy;IRCCS Neuromed, Pozzilli, Italy.
    Concas, Maria Pina
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
    Corre, Tanguy
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland;Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland.
    Cusi, Daniele
    Italy Natl Res Council, Inst Biomed Technol, Milan, Italy;Bio4Dreams, Milan, Italy.
    Felicita, Sala Cinzia
    San Raffaele Res Inst, Milan, Italy.
    de Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
    De Grandi, Alessandro
    Inst Biomed, Eurac Res, Bolzano, Italy.
    de Mutsert, Rene
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands.
    de Vries, Aiko P. J.
    Leiden Univ, Dept Internal Med, Sect Nephrol, Med Ctr, Leiden, Netherlands.
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Mannheim, Germany.
    Demirkan, Ayse
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands;Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
    Devuyst, Olivier
    Univ Zurich, Inst Physiol, Zurich, Switzerland.
    Dittrich, Katalin
    Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Eckardt, Kai-Uwe
    Charit Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Dept Nephrol & Hypertens, Erlangen, Germany.
    Ehret, Georg
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Endlich, Karlhans
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Dept Anat & Cell Biol, Greifswald, Germany.
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
    Gasparini, Paolo
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gieger, Christian
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;German Ctr Diabet Res, Neuherberg, Germany.
    Girotto, Giorgia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Ggele, Martin
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Gordon, Scott D.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
    Gudbjartsson, Daniel F.
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.
    Haller, Toomas
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Hamet, Pavel
    Ctr Hosp Univ Montreal, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada;Medpharmgene, Montreal, PQ, Canada.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Hicks, Andrew A.
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Hofer, Edith
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria.
    Holm, Hilma
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Huang, Wei
    Chinese Natl Human Genome Ctr, Dept Genet, Shanghai Most Key Lab Hlth & Dis Genom, Shanghai, Peoples R China;Shanghai Ind Technol Inst, Shanghai, Peoples R China.
    Hutri-Kahonen, Nina
    Tampere Univ, Dept Clin Chem, Fimlab Labs, Fac Med & Hlth Technol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Dept Pediat, Tampere, Finland.
    Hwang, Shih-Jen
    Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA;NHLBI, Ctr Populat Studies, Framingham, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
    Lewis, Raychel M.
    Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jakobsdottir, Johanna
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland.
    Jonsdottir, Ingileif
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Jonsson, Helgi
    Landspitalinn Univ Hosp, Reykjavik, Iceland;Univ Iceland, Reykjavik, Iceland.
    Joshi, Peter K.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Josyula, Navya Shilpa
    Geisinger Res Biomed & Translat Informat Inst, Rockville, MD USA.
    Jung, Bettina
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Kahonen, Mika
    Tampere Univ, Tampere Univ Hosp, Dept Clin Physiol, Fac Med & Hlth Technol, Tampere, Finland;Tampere Univ, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Hlth Technol, Tampere, Finland.
    Kamatani, Yoichiro
    RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan;Kyoto Univ, Kyoto McGill Int Collaborat Sch Genom Med, Grad Sch Med, Kyoto, Japan.
    Kanai, Masahiro
    RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan;Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA.
    Kerr, Shona M.
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Kiess, Wieland
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Mannheim, Germany.
    Koenig, Wolfgang
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Univ Ulm, Inst Epidemiol & Biostat, Ulm, Germany.
    Kooner, Jaspal S.
    Ealing Gen Hosp, Dept Cardiol, London, England;Imperial Coll Healthcare NHS Trust, Imperial Coll London, London, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth 323, London, England;Imperial Coll London, Natl Heart & Lung Inst, London, England.
    Korner, Antje
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Kovacs, Peter
    Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Leipzig, Germany.
    Kramer, Bernhard K.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Mannheim, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Kuhnel, Brigitte
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany.
    La Bianca, Martina
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Lange, Leslie A.
    Univ Colorado Denver, Div Biomed Informat & Personalized Med, Sch Med, Anschutz Med Campus, Aurora, CO USA.
    Lehne, Benjamin
    Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
    Lehtimaki, Terho
    Tampere Univ, Dept Clin Chem, Fimlab Labs, Fac Med & Hlth Technol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland.
    Liu, Jun
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands;Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Lyytikainen, Leo-Pekka
    Tampere Univ, Dept Clin Chem, Fimlab Labs, Fac Med & Hlth Technol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland.
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
    Marz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Rheumatol Endocrino, Mannheim, Germany;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
    Mascalzoni, Deborah
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Matsuda, Koichi
    Univ Tokyo, Grad Sch Frontier Sci, Lab Clin Genome Sequencing, Tokyo, Japan.
    Meisinger, Christa
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Independent Res Grp Clin Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen UNIKA T Augsburg, Augsburg, Germany.
    Meitinger, Thomas
    German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Milaneschi, Yuri
    Amsterdam Univ Med Ctr, Dept Psychiat, Amsterdam Neurosci, Amsterdam, Netherlands;Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands.
    ODonnell, Christopher J.
    VA Boston Healthcare Syst, Boston, MA USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
    Wilson, Otis D.
    Vanderbilt Univ, Div Nephrol & Hypertens, Med Ctr, Nashville, TN USA.
    Gaziano, J. Michael
    Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA;VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Program, Boston, MA USA.
    Mishra, Pashupati P.
    Tampere Univ, Dept Clin Chem, Fimlab Labs, Fac Med & Hlth Technol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Mononen, Nina
    Tampere Univ, Dept Clin Chem, Fimlab Labs, Fac Med & Hlth Technol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr, Tampere, Finland.
    Montgomery, Grant W.
    Univ Queensland, St Lucia, Qld, Australia.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands;Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands.
    Mueller-Nurasyid, Martina
    German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany;Hosp Ludwig Maximilians Univ Munich, Dept Internal Med Cardiol 1, Munich, Germany.
    Nadkarni, Girish N.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD USA.
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
    Nikus, Kjell
    Tampere Univ Hosp, Heart Ctr, Dept Cardiol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Cardiol, Tampere, Finland.
    Ning, Boting
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Noordam, Raymond
    Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
    O'Connell, Jeffrey R.
    Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
    Olafsson, Isleifur
    Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland.
    Padmanabhan, Sandosh
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Penninx, Brenda W. J. H.
    Amsterdam Univ Med Ctr, Dept Psychiat, Amsterdam Neurosci, Amsterdam, Netherlands;Amsterdam Univ Med Ctr, Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands.
    Perls, Thomas
    Boston Univ, Boston Med Ctr, Dept Med, Geriatr Sect,Sch Med, Boston, MA USA.
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;German Ctr Diabet Res, Neuherberg, Germany;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
    Pirastu, Mario
    Natl Res Council Italy, Inst Genet & Biomed Res, UOS Sassari, Sassari, Italy.
    Pirastu, Nicola
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Pistis, Giorgio
    Univ Hosp Lausanne, Dept Psychiat, Lausanne, Switzerland.
    Polasek, Ozren
    Univ Split, Fac Med, Split, Croatia;Geninfo Ltd, Zagreb, Croatia.
    Ponte, Belen
    Univ Hosp Geneva, Dept Specialties Internal Med, Nephrol Serv, Geneva, Switzerland.
    Porteous, David J.
    Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
    Poulain, Tanja
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Rabelink, Ton J.
    Leiden Univ, Dept Internal Med, Sect Nephrol, Med Ctr, Leiden, Netherlands;Leiden Univ, Einthoven Lab Expt Vasc Res, Med Ctr, Leiden, Netherlands.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland;Univ Turku, Ctr Populat Hlth Res, Turku, Finland;Turku Univ Hosp, Turku, Finland.
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany.
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rizzi, Federica
    Univ Milan, Dept Hlth Sci, Milan, Italy;ePhood SRL, ePhood Sci Unit, Milan, Italy.
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Krajcoviechova, Alena
    Charles Univ Prague, Fac Med 1, Ctr Cardiovasc Prevent, Prague, Czech Republic;Thomayer Hosp, Prague, Czech Republic.
    Cifkova, Renata
    Charles Univ Prague, Fac Med 1, Ctr Cardiovasc Prevent, Prague, Czech Republic;Thomayer Hosp, Prague, Czech Republic;Charles Univ Prague, Fac Med 1, Dept Med 2, Prague, Czech Republic.
    Rueedi, Rico
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy;IRCCS Neuromed, Pozzilli, Italy.
    Ryan, Kathleen A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
    Saba, Yasaman
    Med Univ Graz, Gottfried Schatz Res Ctr Cell Signaling Metab & A, Mol Biol & Biochem, Graz, Austria.
    Salvi, Erika
    Univ Milan, Dept Hlth Sci, Milan, Italy;Fdn IRCCS Ist Neurol Carlo Besta, Neurol Unit, Milan, Italy.
    Schmidt, Helena
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria.
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.
    Shaffer, Christian M.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Smith, Albert, V
    Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Populat Hlth & Genom, Dundee, Scotland.
    Spracklen, Cassandra N.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany.
    Stumvoll, Michael
    Univ Leipzig, Div Endocrinol Nephrol & Rheumatol, Leipzig, Germany.
    Sulem, Patrick
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
    Teren, Andrej
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Heart Ctr Leipzig, Leipzig, Germany.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany.
    Thio, Chris H. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Toniolo, Daniela
    San Raffaele Res Inst, Milan, Italy.
    Tonjes, Anke
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Tremblay, Johanne
    Ctr Hosp Univ Montreal, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada;CHUM, Ctr Rech, Montreal, PQ, Canada.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands.
    Vaccargiu, Simona
    Natl Res Council Italy, Inst Genet & Biomed Res, UOS Sassari, Sassari, Italy.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.
    van Duijn, Cornelia M.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands;Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England;Leiden Univ, Leiden Acad Ctr Drug Res, Leiden, Netherlands.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands;Genomics Plc, Oxford, England.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Vollenweider, Peter
    Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland.
    Waeber, Gerard
    Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland.
    Waldenberger, Melanie
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;Helmholtz Zentrum Munchen, Inst Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
    Whitfield, John B.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
    Wild, Sarah H.
    Univ Edinburgh, Ctr Populat Hlth Sci, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Wilson, James F.
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
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    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
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    Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Ealing Gen Hosp, Dept Cardiol, London, England.
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    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
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    Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland.
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    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
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    Geisinger Res, Biomed & Translat Informat Inst, Danville, PA USA.
    Ho, Kevin
    Geisinger, Kidney Hlth Res Inst, Danville, PA USA;Geisinger, Dept Nephrol, Danville, PA USA.
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    NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA;Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Pramstaller, Peter P.
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Dept Epidemiol,Dept Hlth Serv, Seattle, WA USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Kliniken Sudostbayern AG, Dept Nephrol & Rheumatol, Traunstein, Germany.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Okada, Yukinori
    RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Osaka, Japan;Osaka Univ, Dept Stat Genet, Grad Sch Med, Osaka, Japan.
    Edwards, Todd L.
    Vanderbilt Univ, Vanderbilt Genet Inst, Dept Med, Div Epidemiol,Med Ctr, Nashville, TN USA;Vanderbilt Univ, Dept Vet Affairs, Tennessee Valley Healthcare Syst 626, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Susztak, Katalin
    Univ Penn, Dept Med & Genet, Philadelphia, PA 19104 USA.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Hung, Adriana M.
    Vanderbilt Univ, Div Nephrol & Hypertens, Med Ctr, Nashville, TN USA;Vanderbilt Univ, Dept Vet Affairs, Tennessee Valley Healthcare Syst 626, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Pattaro, Cristian
    Inst Biomed, Eurac Res, Bolzano, Italy.
    Woodward, Owen M.
    Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Koettgen, Anna
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA;Univ Freiburg, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Fac Med, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels2019Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 10, s. 1459-1474Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

  • 226.
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    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Ingram Canc Ctr,Vanderbilt Ep, Nashville, TN 37212 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Univ Texas Sch Publ Hlth, Univ Texas MD Anderson Canc Ctr,UTHealth Grad Sch, Houston, TX 77030 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Fine, Rebecca S.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Bradfield, Jonathan P.
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Quantinuum Res LLC, San Diego, CA USA..
    Esko, Tonu
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Giri, Ayush
    Vanderbilt Univ, Dept Med, Div Epidemiol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN USA..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Hendricks, Audrey E.
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Colorado, Dept Math & Stat Sci, Denver, CO 80202 USA..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Eastern Mediterranean Univ, Fac Arts & Sci, Dept Biol Sci, Gazimagusa, Cyprus..
    Lempradl, Adelheid
    Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA..
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    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Sivapalaratnam, Suthesh
    AMC, Dept Vasc Med, Amsterdam, Netherlands.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Alfred, Tamuno
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Manning, Alisa K.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Vedantam, Sailaja
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherlands Comprehens Canc Org, Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Alam, Dewan S.
    York Univ, Sch Kinesiol & Hlth Sci, Fac Hlth, Toronto, ON, Canada..
    Alharthi, Sameer E.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, Lille, France.;Inst Pasteur, U1167, Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, Lille, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA..
    Balkau, Beverley
    Ctr Rech Epidemiol & Sante Populat CESP, U1018, INSERM, Villejuif, France..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Bastarache, Lisa
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Benn, Marianne
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Epidemiol, Nuthetal, Germany..
    Boerwinkle, Eric
    Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Univ Texas Sch Publ Hlth, Univ Texas MD Anderson Canc Ctr,UTHealth Grad Sch, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London, England.;South London & Maudsley Hosp, NIHR Biomed Res Ctr Mental Hlth, London, England..
    Brilliant, Murray H.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Brumat, Marco
    Univ Trieste, Dept Med Sci, Trieste, Italy..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA USA..
    Butterworth, Adam S.
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England..
    Campbell, Peter T.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA..
    Cappellani, Stefania
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Carey, David J.
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA..
    Catamo, Eulalia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Caulfield, Mark J.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Chambers, John C.
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Chasman, Daniel I.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Chen, Yii-Der I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Chowdhury, Rajiv
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Christensen, Cramer
    Lillebaelt Hosp, Med Dept, Vejle, Denmark..
    Chu, Audrey Y.
    NHLBI Framingham Heart Study, Framingham, MA USA.;Merck Sharp & Dohme Ltd, Genet & Pharmacogen, Boston, MA USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Collins, Francis S.
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Crosslin, David S.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    D'Eustacchio, Angela
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Danesh, John
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Med, British Heart Fdn Cambridge Ctr Excellence, Cambridge, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Utrecht, Netherlands..
    Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands..
    Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Heijer, Martin
    Vrije Univ Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands..
    Hollander, Anneke I.
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands..
    Ruijter, Hester M.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England..
    Denny, Josh C.
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Angelantonio, Emanuele
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA..
    Dube, Marie-Pierre
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Edwards, Todd L.
    Vanderbilt Univ, Dept Med, Div Epidemiol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN USA..
    Ellinghaus, David
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany..
    Ellinor, Patrick T.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England..
    Evangelou, Evangelos
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece.;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Farooqi, I. Sadaf
    Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Fauser, Sascha
    Univ Cologne, Dept Ophthalmol, Cologne, Germany..
    Feng, Shuang
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Ferrannini, Ele
    CNR, Inst Clin Physiol, Pisa, Italy.;Univ Pisa, Dept Clin & Expt Med, Pisa, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Toulouse, France..
    Florez, Jose C.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Ford, Ian
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Franke, Andre
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Friedrich, Nele
    Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.;Univ Med Greifswald, Lab Med, Greifswald, Germany..
    Frikke-Schmidt, Ruth
    Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gandin, Ilaria
    AREA Sci Pk, Res Unit, Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, Trieste, Italy.;IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Gibson, Jane
    Univ Southampton, Fac Nat & Environm Sci, Ctr Biol Sci, Southampton, Hants, England..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Gordon-Larsen, Penny
    Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.;Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Grabe, Hans-Joergen
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.;German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany..
    Grant, Struan F. A.
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Griffiths, Helen L.
    Univ Southampton, Fac Med, Clin Neurosci Res Grp, Vis Sci, Southampton, Hants, England..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Haessler, Jeff
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Hammerschlag, Anke R.
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam Neurosci, Amsterdam, Netherlands..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England..
    Have, Christian T.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC USA.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Heard-Costa, Nancy L.
    NHLBI Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Heath, Andrew C.
    Washington Univ, Dept Psychiat, St Louis, MO USA..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Hu, Yao
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Huffman, Jennifer E.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Res Unit Skelleftea, Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, Frederiksberg, Denmark..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark.;Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Jorgensen, Torben
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.;Aalborg Univ, Fac Med, Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands..
    Kahali, Bratati
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.;Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India..
    Kahn, Rene S.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere, Finland.;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Karaleftheri, Maria
    Echinos Med Ctr, Echinos, Greece..
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Kathiresan, Sekar
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast, Antrim, North Ireland..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Kim, Eric
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Kooner, Jaspal S.
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Korhonen, Tellervo
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany..
    Kuivaniemi, Helena
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Psychiat, Tygerberg, South Africa.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
    Kutalik, Zoltan
    Swiss Inst Bioinformat, Lausanne, Switzerland.;Lausanne Univ Hosp, Inst Social & Prevent Med, Lausanne, Switzerland..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Lamparter, David
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA USA.;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Lee, Nanette R.
    Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines.;Univ San Carlos, USC Off Populat Studies Fdn Inc, Cebu, Philippines..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA..
    Li, Huaixing
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Li, Jin
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Keng-Hung
    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Lo, Ken S.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Lophatananon, Artitaya
    Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry, W Midlands, England..
    Lotery, Andrew J.
    Univ Southampton, Fac Med, Clin Neurosci Res Grp, Vis Sci, Southampton, Hants, England..
    Loukola, Anu
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Lubitz, Steven A.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Hinxton, England..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    McKean-Cowdin, Roberta
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Meidtner, Karina
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mistry, Vanisha
    Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Moilanen, Leena
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland..
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Moore, Carmel
    Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, INTERVAL Coordinating Ctr, Cambridge, England..
    Mori, Trevor A.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia..
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Nalls, Mike A.
    NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA.;Data Tecn Int, Glen Echo, MD USA..
    Narisu, Narisu
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Nikus, Kjell
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Tampere, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Nyholt, Dale R.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA..
    O'Donoghue, Michelle L.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Ophoff, Roel A.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Med Res Inst, Dundee, Scotland..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Peloso, Gina M.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Perry, James A.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Pers, Tune H.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Person, Thomas N.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Peters, Annette
    German Ctr Diabet Res, Neuherberg, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Petersen, Eva R. B.
    Lillebaelt Hosp, Dept Clin Immunol & Biochem, Vejle, Denmark..
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Polasek, Ozren
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Split, Sch Med, Split, Croatia..
    Polderman, Tinca J.
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam Neurosci, Amsterdam, Netherlands..
    Puolijoki, Hannu
    Cent Hosp Southern Ostrobothnia, Seinajoki, Finland..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Rasheed, Asif
    Ctr Noncommun Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland..
    Reilly, Dermot F.
    Merck Sharp & Dohme Ltd, Genet & Pharmacogen, Boston, MA USA..
    Renstrom, Frida
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Rioux, John D.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    Rivas, Manuel A.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Roberts, David J.
    Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;NHS Blood & Transplant Oxford Ctr, Oxford, England.;Univ Oxford, BRC Haematol Theme & Radcliffe Dept Med, Oxford, England..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Saleheen, Danish
    Ctr Noncommun Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Schoen, Robert E.
    Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA.;Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA..
    Schreiner, Pamela J.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Segura-Lepe, Marcelo P.
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Shah, Svati H.
    Duke Univ, Duke Mol Physiol Inst, Durham, NC USA..
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung, Taiwan.;Natl Def Med Ctr, Sch Med, Taipei, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Slater, Andrew J.
    GlaxoSmithKline, Genet, Target Sci, Res Triangle Pk, NC USA.;OmicSoft Qiagen Co, Cary, NC USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Smith, Albert V.
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Southam, Lorraine
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Speliotes, Elizabeth K.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Stumvoll, Michael
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Sun, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC USA.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Surendran, Praveen
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Swift, Amy J.
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Tada, Hayato
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.;Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Tansey, Katherine E.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;Cardiff Univ, Coll Biomed & Life Sci, Cardiff, S Glam, Wales..
    Tardif, Jean-Claude
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England..
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, Leipzig, Germany..
    Tromp, Gerard
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;Dasman Diabet Inst, Dasman, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Uusitupa, Matti
    Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland..
    Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Leeuwen, Nienke
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands..
    Vanhala, Mauno
    Cent Hosp Cent Finland, Primary Hlth Care Unit, Jyvaskyla, Finland.;Kuopio Univ Hosp, Primary Hlth Care Unit, Kuopio, Finland..
    Varbo, Anette
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Dept Ophthalmol, Keck Sch Med, USC Roski Eye Inst, Los Angeles, CA USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Dept Obstet & Gynecol, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Veronesi, Giovanni
    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med, Varese, Italy..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Vogt, Thomas F.
    Merck Sharp & Dohme Ltd, Cardiometabol Dis, Kenilworth, NJ USA..
    Voelker, Uwe
    German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Interfaculty Inst Genet & Funct Gen, Greifswald, Germany..
    Vuckovic, Dragana
    Univ Trieste, Dept Med Sci, Trieste, Italy.;IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Wagenknecht, Lynne E.
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle, NSW, Australia..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wang, Feijie
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Wang, Yiqin
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Ware, Erin B.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Warren, Helen R.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Waterworth, Dawn M.
    GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA USA..
    Wessel, Jennifer
    Indiana Univ, Dept Epidemiol, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Indianapolis, IN 46204 USA.;Indiana Univ, Dept Med, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Indianapolis, IN 46204 USA.;Indiana Univ, Sch Med, Indianapolis, IN USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Willer, Cristen J.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Yao, Pang
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA.;GlaxoSmithKline, King Of Prussia, PA USA..
    Young, Robin
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Glasgow, Glasgow, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Hinxton, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dallas, TX 75390 USA..
    Zhang, Weihua
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Zondervan, Krina T.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford, England..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Pospisilik, John A.
    Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany..
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Lettre, Guillaume
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC USA.;Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England..
    Hirschhorn, Joel N.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 1, s. 26-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  • 227. Ueda, Peter
    et al.
    Cnattingius, Sven
    Stephansson, Olof
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ludvigsson, Jonas F.
    Bonamy, Anna-Karin Edstedt
    Cerebrovascular and ischemic heart disease in young adults born preterm: a population-based Swedish cohort study2014Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, nr 4, s. 253-260Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Preterm birth is associated with overall cardiovascular mortality in young adulthood, but which specific conditions that underlie this association is unknown. We studied mortality and morbidity from cerebrovascular and ischemic heart disease in individuals born preterm. In a nationwide Swedish study, we included 1,306,943 individuals without congenital malformations born between 1983 and 1995, followed from 15 years of age to December 31st, 2010. Of these, 73,489 (5.6 %) were born preterm (< 37 weeks of gestation). Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), after adjusting for maternal characteristics and birth weight for gestational age. Of 955 incident cases of cerebrovascular disease, 58 (6.1 %) occurred in preterm born subjects. The corresponding numbers of ischemic heart disease cases were 180 and 13 (7.2 %), respectively. Birth before 32 weeks was associated with a nearly twofold increased risk of cerebrovascular disease; adjusted HR, (95 % CI) = 1.89 (1.01-3.54) compared to term born individuals, whereas individuals born at 32-36 weeks were not at increased risk. Preterm birth was not associated with later ischemic heart disease; no cases of ischemic heart disease were recorded among those born before 32 weeks and the HR (95 % CI) for those born at 32-36 weeks of gestation was 1.45 (0.81-2.57), compared to term-born individuals. Birth before 32 weeks is associated with increased risk of cerebrovascular disease in young adulthood. Our data suggest that cardiovascular health promotion in follow-up programs after very preterm birth may be beneficial.

  • 228.
    van der Laan, Sander W.
    et al.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Soumare, Aicha
    Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany..
    Sedaghat, Sanaz
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Baumert, Jens
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Zabaneh, Delilah
    UCL, Dept Genet Environm & Evolut, London, England.;UCL, Genet Inst, London, England..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Isgum, Ivana
    Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Arpegard, Johannes
    Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Amouyel, Philippe
    Univ Lille, INSERM, Lille, France.;Inst Pasteur, Lille, France..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Waldenberger, Melanie
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Doerr, Marcus
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Felix, Janine F.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Kavousi, Maryam
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    O'Donnell, Christopher
    Boston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England..
    Malik, Rainer
    Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany..
    Dichgans, Martin
    Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany..
    Worrall, Bradford B.
    Univ Virginia, Dept Neurol, Charlottesville, VA USA.;Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Schunkert, Heribert
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany..
    Marchini, Jonathan
    Univ Oxford, Dept Stat, Oxford, England..
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.;Barts Heart Ctr, London, England.;UCL, Farr Inst Hlth Informat, London, England..
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    de Graaf, Jacqueline
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands..
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Baumeister, Sebastian E.
    Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Koenig, Wolfgang
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany..
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Peters, Annette
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Thorand, Barbara
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands..
    Eriksen, Bjorn Odvar
    UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.;Univ Hosp North Norway, Nephrol Sect, Tromso, Norway..
    Toft, Ingrid
    Univ Hosp North Norway, Nephrol Sect, Tromso, Norway..
    Wilsgaard, Tom
    UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway..
    Onland-Moret, N. Charlotte
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Debette, Stephanie
    Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France..
    Kumari, Meena
    Univ Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England..
    Svensson, Per
    Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    van der Harst, Pim
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Keating, Brendan J.
    Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Sattar, Naveed
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    den Ruijter, Hester M.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Holmes, Michael V.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study2016Inngår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 68, nr 9, s. 934-945Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.

  • 229.
    Varga, Tibor V.
    et al.
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Kurbasic, Azra
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Aine, Mattias
    Lund Univ, Skåne Univ Hosp, Div Oncol & Pathol.
    Eriksson, Pontus
    Lund Univ, Skåne Univ Hosp, Div Oncol & Pathol.
    Ali, Ashfaq
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Hindy, George
    Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Luan, Jian'an
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Shungin, Dmitry
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Odontol;Umeå Univ, Dept Publ Hlth & Clin Med.
    Chen, Yan
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Schulz, Christina-Alexandra
    Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol.
    Nilsson, Peter M.
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci.
    Hallmans, Göran
    Umeå Univ, Dept Biobank Res.
    Barroso, Ines
    Wellcome Trust Sanger Inst.;Addenbrookes Hosp, Metab Res Labs, Cambridge, Hosp, Metab Res Labs; Addenbrookes Hosp, NIHR Cambridge BiomeEngland.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr.
    Deloukas, Panos
    Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah.
    Langenberg, Claudia
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Scott, Robert A.
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Wareham, Nicholas J.
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford.
    Melander, Olle
    Skåne Univ, Dept Clin Sci Hypertens & Cardiovasc Dis.
    Orho-Melander, Marju
    Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol.
    Renström, Frida
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Biobank Res.
    Franks, Paul W.
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Publ Hlth & Clin Med;Harvard TH Chan Sch Publ Hlth, Dept Nutr.
    Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults2017Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, nr 4, s. 1211-1222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.

    Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.

    Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.

    Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.

  • 230. Vasan, Ramachandran S
    et al.
    Glazer, Nicole L.
    Felix, Janine F.
    Lieb, Wolfgang
    Wild, Philipp S.
    Felix, Stephan B.
    Watzinger, Norbert
    Larson, Martin G.
    Smith, Nicholas L.
    Dehghan, Abbas
    Grosshennig, Anika
    Schillert, Arne
    Teumer, Alexander
    Schmidt, Reinhold
    Kathiresan, Sekar
    Lumley, Thomas
    Aulchenko, Yurii S.
    König, Inke R.
    Zeller, Tanja
    Homuth, Georg
    Struchalin, Maksim
    Aragam, Jayashri
    Bis, Joshua C.
    Rivadeneira, Fernando
    Erdmann, Jeanette
    Schnabel, Renate B.
    Dörr, Marcus
    Zweiker, Robert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Rodeheffer, Richard J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Greiser, Karin Halina
    Levy, Daniel
    Haritunians, Talin
    Deckers, Jaap W.
    Stritzke, Jan
    Lackner, Karl J.
    Völker, Uwe
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kullo, Iftikhar
    Haerting, Johannes
    O'Donnell, Christopher J.
    Heckbert, Susan R.
    Stricker, Bruno H.
    Ziegler, Andreas
    Reffelmann, Thorsten
    Redfield, Margaret M.
    Werdan, Karl
    Mitchell, Gary F.
    Rice, Kenneth
    Arnett, Donna K.
    Hofman, Albert
    Gottdiener, John S.
    Uitterlinden, Andre G.
    Meitinger, Thomas
    Blettner, Maria
    Friedrich, Nele
    Wang, Thomas J.
    Psaty, Bruce M.
    van Duijn, Cornelia M.
    Wichmann, H-Erich
    Munzel, Thomas F.
    Kroemer, Heyo K.
    Benjamin, Emelia J.
    Rotter, Jerome I.
    Witteman, Jacqueline C.
    Schunkert, Heribert
    Schmidt, Helena
    Völzke, Henry
    Blankenberg, Stefan
    Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data2009Inngår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 302, nr 2, s. 168-178Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

  • 231. Vasan, S K
    et al.
    Fall, Tove
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Job, V
    Gu, H F
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Brismar, K
    Karpe, F
    Thomas, N
    A common variant in the FTO locus is associated with waist-hip ratio in Indian adolescents2013Inngår i: Pediatric obesity, ISSN 2047-6310, Vol. 8, nr 3, s. e45-e49Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Common variants in the FTO locus, and near MC4R locus, have been shown to have a robust association with obesity in children and adults among various ethnic groups. Associations with obesity traits among Indian adolescents have not been determined.

    OBJECTIVE: To study the association of rs9939609 (FTO) and rs17782313 (MC4R) to obesity related anthropometric traits in Indian adolescents.

    METHODS: Subjects for the current study were recruited from a cross-sectional cohort of 1,230 adolescents (age mean ± SD: 17.1 ± 1.9 years) from South India.

    RESULTS: The variant at the FTO locus was found to be associated with waist-hip ratio (WHR) but not with overall obesity in this population. No significant association was observed for obesity-traits and Mc4R variant rs17782313.

    CONCLUSION: The common variant of FTO (rs9939609) is associated with body fat distribution during early growth in Indian adolescents and may predispose to obesity and metabolic consequences in adulthood.

  • 232. Vasan, Senthil K
    et al.
    Fall, Tove
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Neville, Matthew J
    Antonisamy, Belavendra
    Fall, Caroline H
    Geethanjali, Finney S
    Gu, Harvest F
    Raghupathy, Palany
    Samuel, Prasanna
    Thomas, Nihal
    Brismar, Kerstin
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Karpe, Fredrik
    Associations of variants in FTO and near MC4R with obesity traits in South Asian Indians2012Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 20, nr 11, s. 2268-2277Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist-hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian "thin-fat" phenotype.

  • 233. Vasan, Senthil K.
    et al.
    Karpe, Fredrik
    Gu, Harvest F.
    Brismar, Kerstin
    Fall, Caroline H.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    FTO Genetic Variants and Risk of Obesity and Type 2 Diabetes: A Meta-Analysis of 28,394 Indians2014Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, nr 3, s. 964-970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the magnitude of association of FTO variants with obesity, type 2 diabetes (T2DM), and related traits among Asian Indians. Methods: Random-effect meta-analysis was performed on pooled data from eight studies (n=28,394) for obesity and related traits and six studies (n=24,987) for assessment of T2DM risk in Indians where FTO variants were reported. Results: The minor A-allele of the FTO variant rs9939609 was associated with increased risk of obesity (OR 1.15, 95% CI 1.08-1.21, p=2.14 3 10 25), BMI (b=0.30 kg/m 2, 95% CI 0.21-0.38, p=4.78 3 10211) and other regional adiposity measurements [waist (b50.74 cm, 95% CI 0.49-0.99), HC (b=0.52, 95% CI 0.26-0.78), and waist-hip ratio (WHR) (b50.002, 95% CI 0.001-0.004)] in Indians (p = 0.001). An increased risk for T2DM (OR 1.11; 95% CI 1.04-1.19, p=0.002) was observed, which attenuated when adjusted for age, gender, and BMI (OR 1.09; 95% CI 1.02-1.16, p=0.01). Conclusions: Our study provides evidence of association between common FTO variant and obesity risk among Indians with comparable effect sizes as in Caucasians. The attenuation of FTO-T2DM risk on BMI adjustment reinforces that BMI does not fully account for the adiposity effects among Asian Indians who are more centrally obese.

  • 234. Vimaleswaran, Karani S
    et al.
    Cavadino, Alana
    Berry, Diane J
    Jorde, Rolf
    Dieffenbach, Aida Karina
    Lu, Chen
    Alves, Alexessander Couto
    Heerspink, Hiddo J Lambers
    Tikkanen, Emmi
    Eriksson, Joel
    Wong, Andrew
    Mangino, Massimo
    Jablonski, Kathleen A
    Nolte, Ilja M
    Houston, Denise K
    Ahluwalia, Tarunveer Singh
    van der Most, Peter J
    Pasko, Dorota
    Zgaga, Lina
    Thiering, Elisabeth
    Vitart, Veronique
    Fraser, Ross M
    Huffman, Jennifer E
    de Boer, Rudolf A
    Schöttker, Ben
    Saum, Kai-Uwe
    McCarthy, Mark I
    Dupuis, Josée
    Herzig, Karl-Heinz
    Sebert, Sylvain
    Pouta, Anneli
    Laitinen, Jaana
    Kleber, Marcus E
    Navis, Gerjan
    Lorentzon, Mattias
    Jameson, Karen
    Arden, Nigel
    Cooper, Jackie A
    Acharya, Jayshree
    Hardy, Rebecca
    Raitakari, Olli
    Ripatti, Samuli
    Billings, Liana K
    Lahti, Jari
    Osmond, Clive
    Penninx, Brenda W
    Rejnmark, Lars
    Lohman, Kurt K
    Paternoster, Lavinia
    Stolk, Ronald P
    Hernandez, Dena G
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mellström, Dan
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Tzoulaki, Ioanna
    McLachlan, Stela
    Theodoratou, Evropi
    Tiesler, Carla M T
    Jula, Antti
    Navarro, Pau
    Wright, Alan F
    Polasek, Ozren
    Wilson, James F
    Rudan, Igor
    Salomaa, Veikko
    Heinrich, Joachim
    Campbell, Harry
    Price, Jacqueline F
    Karlsson, Magnus
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bandinelli, Stefania
    Frayling, Timothy M
    Hartman, Catharina A
    Sørensen, Thorkild I A
    Kritchevsky, Stephen B
    Langdahl, Bente Lomholt
    Eriksson, Johan G
    Florez, Jose C
    Spector, Tim D
    Lehtimäki, Terho
    Kuh, Diana
    Humphries, Steve E
    Cooper, Cyrus
    Ohlsson, Claes
    März, Winfried
    de Borst, Martin H
    Kumari, Meena
    Kivimaki, Mika
    Wang, Thomas J
    Power, Chris
    Brenner, Hermann
    Grimnes, Guri
    van der Harst, Pim
    Snieder, Harold
    Hingorani, Aroon D
    Pilz, Stefan
    Whittaker, John C
    Järvelin, Marjo-Riitta
    Hyppönen, Elina
    Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study2014Inngår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 2, nr 9, s. 719-729Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

    METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

    FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

    INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

  • 235. Voight, Benjamin F
    et al.
    Peloso, Gina M
    Orho-Melander, Marju
    Frikke-Schmidt, Ruth
    Barbalic, Maja
    Jensen, Majken K
    Hindy, George
    Hólm, Hilma
    Ding, Eric L
    Johnson, Toby
    Schunkert, Heribert
    Samani, Nilesh J
    Clarke, Robert
    Hopewell, Jemma C
    Thompson, John F
    Li, Mingyao
    Thorleifsson, Gudmar
    Newton-Cheh, Christopher
    Musunuru, Kiran
    Pirruccello, James P
    Saleheen, Danish
    Chen, Li
    Stewart, Alexandre F R
    Schillert, Arne
    Thorsteinsdottir, Unnur
    Thorgeirsson, Gudmundur
    Anand, Sonia
    Engert, James C
    Morgan, Thomas
    Spertus, John
    Stoll, Monika
    Berger, Klaus
    Martinelli, Nicola
    Girelli, Domenico
    McKeown, Pascal P
    Patterson, Christopher C
    Epstein, Stephen E
    Devaney, Joseph
    Burnett, Mary-Susan
    Mooser, Vincent
    Ripatti, Samuli
    Surakka, Ida
    Nieminen, Markku S
    Sinisalo, Juha
    Lokki, Marja-Liisa
    Perola, Markus
    Havulinna, Aki
    de Faire, Ulf
    Gigante, Bruna
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Zeller, Tanja
    Wild, Philipp
    de Bakker, Paul I W
    Klungel, Olaf H
    Maitland-van der Zee, Anke-Hilse
    Peters, Bas J M
    de Boer, Anthonius
    Grobbee, Diederick E
    Kamphuisen, Pieter W
    Deneer, Vera H M
    Elbers, Clara C
    Onland-Moret, N Charlotte
    Hofker, Marten H
    Wijmenga, Cisca
    Verschuren, W M Monique
    Boer, Jolanda M A
    van der Schouw, Yvonne T
    Rasheed, Asif
    Frossard, Philippe
    Demissie, Serkalem
    Willer, Cristen
    Do, Ron
    Ordovas, Jose M
    Abecasis, Gonçalo R
    Boehnke, Michael
    Mohlke, Karen L
    Daly, Mark J
    Guiducci, Candace
    Burtt, Noël P
    Surti, Aarti
    Gonzalez, Elena
    Purcell, Shaun
    Gabriel, Stacey
    Marrugat, Jaume
    Peden, John
    Erdmann, Jeanette
    Diemert, Patrick
    Willenborg, Christina
    König, Inke R
    Fischer, Marcus
    Hengstenberg, Christian
    Ziegler, Andreas
    Buysschaert, Ian
    Lambrechts, Diether
    Van de Werf, Frans
    Fox, Keith A
    El Mokhtari, Nour Eddine
    Rubin, Diana
    Schrezenmeir, Jürgen
    Schreiber, Stefan
    Schäfer, Arne
    Danesh, John
    Blankenberg, Stefan
    Roberts, Robert
    McPherson, Ruth
    Watkins, Hugh
    Hall, Alistair S
    Overvad, Kim
    Rimm, Eric
    Boerwinkle, Eric
    Tybjaerg-Hansen, Anne
    Cupples, L Adrienne
    Reilly, Muredach P
    Melander, Olle
    Mannucci, Pier M
    Ardissino, Diego
    Siscovick, David
    Elosua, Roberto
    Stefansson, Kari
    O'Donnell, Christopher J
    Salomaa, Veikko
    Rader, Daniel J
    Peltonen, Leena
    Schwartz, Stephen M
    Altshuler, David
    Kathiresan, Sekar
    Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study2012Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 380, nr 9841, s. 572-580Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.

    METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.

    FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).

    INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.

  • 236.
    Wain, Louise V.
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    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Tehran, Iran..
    Jansen, Rick
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Joehanes, Roby
    Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA.;Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Erzurumluoglu, A. Mesut
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    O'Reilly, Paul F.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England. Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Cabrera, Claudia P.
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Warren, Helen R.
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Verwoert, Germaine C.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Hottenga, Jouke-Jan
    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ, Ctr Mol Med, Solna, Sweden..
    Esko, Tonu
    Childrens Hosp, Div Endocrinol, Boston, MA USA.;Broad Inst Harvard & MIT, Cambridge, MA USA..
    Arking, Dan E.
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA..
    Hwang, Shih-Jen
    NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA USA..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Shrine, Nick
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Smith, Albert V.
    Icelandic Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Amin, Najaf
    Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands..
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere, Finland..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
    Joshi, Peter K.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Kristiansson, Kati
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Traglia, Michela
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Havulinna, Aki S.
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, Bethesda, MD 20892 USA.;Data Tecn Int, Glen Echo, MD USA..
    Sober, Siim
    Univ Tartu, Inst Biomed & Translat Med, Tartu, Estonia..
    Vuckovic, Dragana
    IRCCS Burlo Garofolo Children Hosp, Med Genet, Trieste, Italy.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Del Greco M, Fabiola
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy..
    Ayers, Kristin L.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA..
    Marrugat, Jaume
    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain.;CIBERCV, Barcelona, Spain..
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy..
    Lopez, Lorna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Beaumont Hosp, Dept Psychiat, Royal Coll Surg Ireland, Educ & Res Ctr, Dublin, Ireland.;Univ Coll Dublin, UCD Conway Inst, Ctr Proteome Res, Belfield, Ireland.;Univ Coll Dublin, Sch Med, Conway Inst, Belfield, Ireland..
    Niiranen, Teemu
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Enroth, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI USA..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Univ Leicester, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Huffman, Jennifer E.
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Southall, Middx, England..
    Marten, Jonathan
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Gandin, Ilaria
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Zemunik, Tatijana
    London North West Healthcare NHS Trust, Dept Med Biol, Fac Med, Southall, Middx, England..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA..
    Evangelou, Evangelos
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina, Greece..
    Shah, Nabi
    Univ Dundee, Med Res Inst, Ninewells Hosp, Dundee, Scotland.;Univ Dundee, Sch Med, Dundee, Scotland.;COMSATS Inst Informat Technol, Dept Pharm, Abbottabad, Pakistan..
    de Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands..
    Mangino, Massimo
    Natl Inst Hlth Res, Biomed Res Ctr, London, England..
    Prins, Bram P.
    Wellcome Trust Sanger Inst, Dept Human Genet, London, England..
    Campbell, Archie
    Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
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    Bordeaux Populat Hlth Ctr, INSERM U 1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France..
    Oldmeadow, Christopher
    Hunter Med Res Inst, New Lambton, NSW, Australia..
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    Ctr Stat Genet, Dept Biostat, Ann Arbor, MI USA..
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    Isfahan Univ Med Sci, Dept Genet & Mol Biol, Esfahan, Iran..
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    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
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    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Batini, Chiara
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Beilby, John
    Busselton Populat Med Res Inst, Nedlands, WA, Australia.;PathWest Lab Med Western Australia, Nedlands, WA, Australia.;Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA, Australia..
    Blake, Tineka
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI USA..
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA..
    Braund, Peter S.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Univ Leicester, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Brown, Morris
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Brumat, Marco
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Campbell, Harry
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Collins, Francis
    NHGRI, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Connell, John
    Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Cordell, Heather J.
    Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England..
    Damman, Jeffrey J.
    Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    de Geus, Eco J.
    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Deelen, Joris
    Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands..
    Demirkale, Yusuf
    NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA..
    Doney, Alex S. F.
    Univ Dundee, Med Res Inst, Ninewells Hosp, Dundee, Scotland.;Univ Dundee, Sch Med, Dundee, Scotland..
    Dorr, Marcus
    Univ Med Greifswald, Dept Internal Med, Greifswald, Germany.;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Farrall, Martin
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England..
    Ferreira, Teresa
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Franberg, Mattias
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ, Ctr Mol Med, Solna, Sweden.;Stockholm Univ, Dept Numer Anal & Comp Sci, Stockholm, Sweden..
    Gao, He
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gieger, Christian
    Forschungszentrum Gesundheit & Umwelt GmbH, Neuherberg, Germany..
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Gow, Alan J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Heriot Watt Univ, Sch Social Sci, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ, Ctr Mol Med, Solna, Sweden..
    Harris, Tamara B.
    NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Holliday, Elizabeth G.
    Hunter Med Res Inst, New Lambton, NSW, Australia..
    Hui, Jennie
    Busselton Populat Med Res Inst, Nedlands, WA, Australia.;PathWest Lab Med Western Australia, Nedlands, WA, Australia.;Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA, Australia.;Univ Western Australia, Sch Populat & Global Hlth, Nedlands, WA, Australia..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
    Johansson, Åsa
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA.;NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bldg 10, Bethesda, MD 20892 USA..
    Jousilahti, Pekka
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Jula, Antti
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.;Univ Tampere, Dept Clin Physiol, Fac Med & Life Sci, Tampere, Finland..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England..
    Kolcic, Ivana
    Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia..
    Koskinen, Seppo
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Larson, Marty
    Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA..
    Launer, Lenore J.
    NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Lin, Li
    Univ Hosp Geneva, Dept Med Specialties, Cardiol, Geneva, Switzerland..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Mach, Francois
    Univ Hosp Geneva, Dept Med Specialties, Cardiol, Geneva, Switzerland..
    Mamasoula, Chrysovalanto
    Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England..
    Menni, Cristina
    Mifsud, Borbala
    William Harvey Res Inst, Clin Pharmacol, London, England..
    Milaneschi, Yuri
    Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands..
    Morgan, Anna
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Morris, Andrew D.
    Univ Edinburgh, Sch Mol Genet & Populat Hlth Sci, Sch Med, Teviot Pl, Edinburgh, Midlothian, Scotland..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Houston, TX USA..
    Munson, Peter J.
    NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA..
    Nandakumar, Priyanka
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA..
    Nguyen, Quang Tri
    Nutile, Teresa
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy..
    Oldehinkel, Albertine J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Oostra, Ben A.
    Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands..
    Org, Elin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Padmanabhan, Sandosh
    Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci,Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.;Univ Glasgow, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland..
    Palotie, Aarno
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands..
    Poulter, Neil
    Imperial Coll London, Sch Publ Hlth, London, England..
    Pramstaller, Peter P.
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy.;Dept Neurol, Gen Cent Hosp, Bolzano, Italy.;Univ Lubeck, Dept Neurol, Lubeck, Germany..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Ren, Meixia
    William Harvey Res Inst, Clin Pharmacol, London, England.;Fujian Med Univ, Fujian Prov Hosp, Dept Cardiol, Fuzhou, Fujian, Peoples R China..
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Riese, Harriette
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Robino, Antonietta
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat & Med, LABioMed, Torrance, CA USA..
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Saba, Yasaman
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
    Saint Pierre, Aude
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy.;INSERM U1078, Etab Francais Sang, Brest, France..
    Sala, Cinzia F.
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Sarin, Antti-Pekka
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
    Scott, Rodney
    Hunter Med Res Inst, New Lambton, NSW, Australia.;Univ Newcastle, Fac Hlth, Callaghan, NSW, Australia.;John Hunter Hosp, New Lambton, NSW, Australia..
    Seelen, Marc A.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands..
    Shields, Denis C.
    Univ Coll Dublin, Sch Med, Conway Inst, Belfield, Ireland..
    Siscovick, David
    New York Acad Med, New York, NY USA..
    Sorice, Rossella
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Stanton, Alice
    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin 2, Ireland..
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Swertz, Morris
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst, Torrance, CA USA.;Harbor UCLA Med Ctr, Div Genet Outcomes, Dept Pediat, Torrance, CA USA..
    Thom, Simon
    Imperial Coll London, Int Ctr Circulatory Hlth, London, England..
    Tzoulaki, Ioanna
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Tzourio, Christophe
    Bordeaux Populat Hlth Ctr, INSERM U 1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France.;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Volker, Uwe
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Vollenweider, Peter
    Univ Lausanne Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland..
    Wild, Sarah
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Willemsen, Gonneke
    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Wright, Alan F.
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Yao, Jie
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA USA..
    Theriault, Sebastien
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Conen, David
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Attia, John
    Hunter Med Res Inst, New Lambton, NSW, Australia.;Univ Newcastle, Fac Hlth, Callaghan, NSW, Australia.;John Hunter Hosp, New Lambton, NSW, Australia..
    Sever, Peter
    Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Debette, Stephanie
    Bordeaux Populat Hlth Ctr, INSERM U 1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, London, England..
    Spector, Tim D.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Palmer, Colin N. A.
    Univ Dundee, Med Res Inst, Ninewells Hosp, Dundee, Scotland.;Univ Dundee, Sch Med, Dundee, Scotland..
    Vergnaud, Anne-Claire
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Loos, Ruth J. F.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY USA..
    Polasek, Ozren
    Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Girotto, Giorgia
    IRCCS Burlo Garofolo Children Hosp, Med Genet, Trieste, Italy.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Hayward, Caroline
    Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England..
    Lindgren, Cecila M.
    Broad Inst Harvard & MIT, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Vitart, Veronique
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Univ Leicester, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Tuomilehto, Jaakko
    Dasman Diabet Inst, Kuwait, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems An Der Donau, Austria. Univ Manchester, Div Cardiovasc Sci, Manchester, Lancs, England..
    Gyllensten, Ulf
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Knekt, Paul
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Ciullo, Marina
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Elosua, Roberto
    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain.;CIBERCV, Barcelona, Spain..
    Keavney, Bernard D.
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    Hicks, Andrew A.
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy..
    Scott, Robert A.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Gasparini, Paolo
    IRCCS Burlo Garofolo Children Hosp, Med Genet, Trieste, Italy.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Laan, Maris
    Univ Tartu, Inst Biomed & Translat Med, Tartu, Estonia..
    Liu, YongMei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Watkins, Hugh
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Salomaa, Veikko
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Toniolo, Daniela
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Wilson, James F.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Schmidt, Helena
    Med Univ Graz, Dept Neurol, Graz, Austria.;Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
    Zhao, Jing Hua
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere, Finland..
    van Duijn, Cornelia M.
    Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands..
    Gudnason, Vilmundur
    Icelandic Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.;Kaiser Permanent, Washington Hlth Res Inst, Seattle, WA USA..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany..
    James, Alan
    Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA, Australia.;Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep, Nedlands, WA, Australia..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London, England..
    Palmas, Walter
    Columbia Univ, Dept Med, Med Ctr, New York, NY USA..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Boomsma, Dorret I.
    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Bochud, Murielle
    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland..
    Newton-Cheh, Christopher
    Broad Inst Harvard & MIT, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Munroe, Patricia B.
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Elliott, Paul
    Imperial Coll London, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Chakravarti, Aravinda
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA..
    Knight, Joanne
    Univ Lancaster, Data Sci Inst, Lancaster, England.;Univ Lancaster, Lancaster Med Sch, Lancaster, England..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Levy, Daniel
    NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Tobin, Martin D.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Caulfield, Mark J.
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Ehret, Georg B.
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA.;Univ Hosp Geneva, Dept Med Specialties, Cardiol, Geneva, Switzerland..
    Alistair, T. Y.
    Betholdson, J. -P
    Xiao, Limin
    Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney2017Inngår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 70, nr 3, s. E4-e19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

  • 237.
    Wang, Yunzhang
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Zhang, Qian
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Almgren, Malin
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Stockholm, Sweden.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.
    McRae, Allan F.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
    Marioni, Riccardo E.
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Visscher, Peter M.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia;Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia.
    Deary, Ian J.
    Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Morris, Tiffany
    UCL, Canc Inst, London, England.
    Beck, Stephan
    UCL, Canc Inst, London, England.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins2018Inngår i: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 13, nr 9, s. 975-987Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3x10(-7)) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9x10(-5)), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1x10(-5)) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.

  • 238.
    Warensjö, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lundmark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity2007Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 15, nr 7, s. 1732-1740Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme A-desaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans.

    RESEARCH METHODS AND PROCEDURES:

    The study population was 1143 elderly Swedish men taking part of a population-based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis.

    RESULTS:

    Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (beta)=1.19, p=0.007] and waist circumference (beta=-4.4, p=0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference.

    CONCLUSION:

    This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.

  • 239.
    Warren, Helen R.
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece..
    Cabrera, Claudia P.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Gao, He
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Ren, Meixia
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Fujian Med Univ, Fujian Prov Hosp, Dept Cardiol, Fuzhou, Peoples R China..
    Mifsud, Borbala
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Ntalla, Ioanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Liu, Chunyu
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;Boston Univ, Sch Publ Hlth, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Kraja, Aldi T.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA..
    Drenos, Fotios
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Loh, Marie
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;ASTAR, Translat Lab Genet Med, Singapore, Singapore..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Marten, Jonathan
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Karaman, Ibrahim
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Lepe, Marcelo P. Segura
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Bayer Pharma, Berlin, Germany..
    O'Reilly, Paul F.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Knight, Joanne
    Univ Lancaster, Data Sci Inst, Lancaster, England..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Kato, Norihiro
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan..
    He, Jiang
    Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA..
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Said, M. Abdullah
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Porteous, David
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Poulter, Neil
    Farrall, Martin
    Univ Oxford, Radcliffe Dept Med, Wellcome Trust Ctr Human Genet, Div Cardiovasc Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands..
    Padmanabhan, Sandosh
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.;Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Stanton, Alice
    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland..
    Connell, John
    Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Bakker, Stephan J. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Shields, Denis C.
    Univ Coll Dublin, Conway Inst, Sch Med, Dublin, Ireland..
    Thom, Simon
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll London, Int Ctr Circulatory Hlth, London, England..
    Brown, Morris
    Sever, Peter
    Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Esko, Tonu
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England.;Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA.;Broad Inst Harvard & MIT, Cambridge, England..
    Hayward, Caroline
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommun Dis, Karachi, Pakistan.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Chasman, Daniel I.
    Chakravarti, Aravinda
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Newton-Cheh, Christopher
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst Harvard & MIT, Cambridge, England..
    Lindgren, Cecilia M.
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Levy, Daniel
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;NHLBI, Framingham Heart Study, Framingham, MA USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Kooner, Jaspal S.
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Keavney, Bernard
    Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England.;Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Div Med, Manchester, Lancs, England..
    Tomaszewski, Maciej
    Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England.;Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Div Med, Manchester, Lancs, England..
    Samani, Nilesh J.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Munroe, Patricia B.
    Ehret, Georg B.
    Wain, Louise V.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Barnes, Michael R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Tzoulaki, Joanna
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommun Dis, Esfahan, Iran..
    Jansen, Rick
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Joehanes, Roby
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Erzurumluoglu, A. Mesut
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    O'Reilly, Paul
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Verwoert, Germaine C.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Hottenga, Jouke-Jan
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Sjukhuset, Ctr Mol Med, Solna, Sweden..
    Arking, Dan E.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Hwang, Shih-Jen
    NHLBI, Populat Sci Branch, US NIH, Bldg 10, Bethesda, MD 20892 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Shrine, Nick
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Hofer, Edith
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Kristiansson, Kati
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Traglia, Michela
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, US NIH, Bethesda, MD 20892 USA.;Kelly Serv, Rockville, MD USA..
    Sober, Siim
    Univ Tartu, Inst Mol & Cell Biol, Human Mol Genet Res Grp, Tartu, Estonia..
    Vuckovic, Dragana
    Sidra Med & Res Ctr, Expt Genet Div, Doha, Qatar.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Del Greco M, Fabiola
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Lubeck, Germany..
    Ayers, Kristin L.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Marrugat, Jaume
    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain..
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys Buzzati Traverso, Naples, Italy..
    Lopez, Lorna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Beaumont Hosp, Educ & Res Ctr, Royal Coll Surg Ireland, Dept Psychiat, Dublin, Ireland.;UCD, Ctr Proteome Res, UCD Conway Inst, Dublin, Ireland..
    Niiranen, Teemu
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Enroth, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, BHF Cardiovasc Res Ctr, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Huffman, Jennifer E.
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Gandin, Ilaria
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Harris, Sarah E.
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland..
    Zemonik, Tatijana
    Univ Split, Fac Med, Dept Biol, Split, Croatia..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Shah, Nabi
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland.;COMSATS Inst Informat Technol, Dept Pharm, Abbottabad, Pakistan..
    de Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Natl Inst Hlth Res, Biomed Res Ctr, London, England..
    Prins, Bram P.
    Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Chauhan, Ganesh
    Bordeaux Populat Hlth Ctr, INSERM, U1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France..
    Oldmeadow, Christopher
    Hunter Med Res Inst, New Lambton, NSW, Australia..
    Abecasis, Goncalo
    SPH II, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Abedi, Maryam
    Isfahan Univ Med Sci, Dept Genet & Mol Biol, Esfahan, Iran..
    Barbieri, Caterina M.
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Batini, Chiara
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Blake, Tineka
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Braund, Peter S.
    Univ Leicester, Glenfield Hosp, BHF Cardiovasc Res Ctr, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Brumat, Marco
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Collins, Francis
    NHGRI, Med Genom & Metab Genet Branch, US NIH, Bethesda, MD 20892 USA..
    Cordell, Heather J.