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  • 151. Mahajan, Anubha
    et al.
    Sim, Xueling
    Ng, Hui Jin
    Manning, Alisa
    Rivas, Manuel A
    Highland, Heather M
    Locke, Adam E
    Grarup, Niels
    Im, Hae Kyung
    Cingolani, Pablo
    Flannick, Jason
    Fontanillas, Pierre
    Fuchsberger, Christian
    Gaulton, Kyle J
    Teslovich, Tanya M
    Rayner, N William
    Robertson, Neil R
    Beer, Nicola L
    Rundle, Jana K
    Bork-Jensen, Jette
    Ladenvall, Claes
    Blancher, Christine
    Buck, David
    Buck, Gemma
    Burtt, Noël P
    Gabriel, Stacey
    Gjesing, Anette P
    Groves, Christopher J
    Hollensted, Mette
    Huyghe, Jeroen R
    Jackson, Anne U
    Jun, Goo
    Justesen, Johanne Marie
    Mangino, Massimo
    Murphy, Jacquelyn
    Neville, Matt
    Onofrio, Robert
    Small, Kerrin S
    Stringham, Heather M
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Trakalo, Joseph
    Abecasis, Goncalo
    Bell, Graeme I
    Blangero, John
    Cox, Nancy J
    Duggirala, Ravindranath
    Hanis, Craig L
    Seielstad, Mark
    Wilson, James G
    Christensen, Cramer
    Brandslund, Ivan
    Rauramaa, Rainer
    Surdulescu, Gabriela L
    Doney, Alex S F
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Linneberg, Allan
    Isomaa, Bo
    Tuomi, Tiinamaija
    Jørgensen, Marit E
    Jørgensen, Torben
    Kuusisto, Johanna
    Uusitupa, Matti
    Salomaa, Veikko
    Spector, Timothy D
    Morris, Andrew D
    Palmer, Colin N A
    Collins, Francis S
    Mohlke, Karen L
    Bergman, Richard N
    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.
    Tuomilehto, Jaakko
    Hansen, Torben
    Watanabe, Richard M
    Prokopenko, Inga
    Dupuis, Josee
    Karpe, Fredrik
    Groop, Leif
    Laakso, Markku
    Pedersen, Oluf
    Florez, Jose C
    Morris, Andrew P
    Altshuler, David
    Meigs, James B
    Boehnke, Michael
    McCarthy, Mark I
    Lindgren, Cecilia M
    Gloyn, Anna L
    Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus2015Inngår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, nr 1, artikkel-id e1004876Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

  • 152.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Taliun, Daniel
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thurner, Matthias
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Robertson, Neil R.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Torres, Jason M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Rayner, N. William
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Payne, Anthony J.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Steinthorsdottir, Valgerdur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Grarup, Niels
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Schmidt, Ellen M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Sarnowski, Chloe
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Magill, Reedik
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Nano, Jana
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Gieger, Christian
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Trompet, Stella
    Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands;Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Prins, Bram Peter
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Below, Jennifer E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Div Genome Res, Chungcheongbuk Do, South Korea.
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Petty, Lauren E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Sim, Xueling
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England.
    Bennett, Amanda J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Bork-Jensen, Jette
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Brummett, Chad M.
    Univ Michigan, Dept Anesthesiol, Med Sch, Ann Arbor, MI 48109 USA.
    Canouil, Mickael
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Kardt, Kai-Uwe Ec
    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany;Charite Univ Med Berlin, German Chron Kidney Dis Study, Berlin, Germany.
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia;Univ Tartu, Inst Math & Stat, Tartu, Estonia.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Locke, Adam E.
    Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA;Washington Univ, Sch Med, Dept Med, Div Genom & Bioinformat, St Louis, MO 63110 USA.
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Ntalla, Loanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
    Nylander, Vibe
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Schoenherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Yengo, Loic
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
    Christensen, Cramer
    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Florez, Jose C.
    Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Diabet Res Ctr, Dept Med, Diabet Unit, Boston, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    France, Oscar H.
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hackinger, Sophie
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Herder, Christian
    German Ctr Diabet Res DZD, Neuherberg, Germany;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Inst Clin Diabetol, Leibniz Ctr Diabet Res, Dusseldorf, Germany.
    Ikram, M. Arfan
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Jorgensen, Marit E.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Ligthart, Symen
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England.
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Frederiksberg, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Lyssenko, Valeriya
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Clin Res Ctr, Ctr Mol Med, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Nadkarni, Girish
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Kuwait, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA;NHLBI, Framingham Heart Stud, Framingham, MA USA.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, 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.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, 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, Stanford, CA USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Groop, Leif
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Collins, Francis S.
    NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
    Grallert, Harald
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Helmholtz Zentrum Munchen, Clin Cooparat Grp Type Diabet 2, Munich, Germany;Tech Univ, Helmholtz Zentrum Munchen, Clin Cooparat Grp, Nutrigen & Type Diabet 2, Munich, Germany.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Dehghan, Abbas
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Koettgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
    Rotter, Jerome, I
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Med, LABioMed, Torrance, CA 90509 USA.
    Marchini, Jonathan
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Pedersen, Oluf
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Hansen, Torben
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gloyn, Anna L.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Morris, Andrew P.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    McCarthy, Mark, I
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 11, s. 1505-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
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    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Zhao, Wei
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Chu, Audrey Y.
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
    Gan, Wei
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
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    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
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    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Univ Utah, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
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    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
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    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
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    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England.
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    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
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    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
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    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Trubetskoy, Vassily Vladimirovich
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
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    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
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    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Mueller-Nurasyid, Martina
    Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany.
    Meidtner, Karina
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
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    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden.
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    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
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    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
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    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
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    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Malerba, Giovanni
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
    Demirkan, Ayse
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
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    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Preuss, Michael
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
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    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
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    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA.
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    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
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    Penn State Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA.
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    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
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    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
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    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Amin, Najaf
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
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    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC USA.
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    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
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    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
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    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
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    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
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    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
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    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
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    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
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    UCL, Inst Cardiovasc Sci, London, England.
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    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany.
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    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
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    Univ Cattolica Sacro Cuore, Inst Internal & Geriatr Med, Rome, Italy.
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    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
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    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
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    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
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    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
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    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA;Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada.
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    Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
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    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
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    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Res Ctr Prevent & Hlth, Glostrup, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland;Vaasa Hlth Care Ctr, Diabet Ctr, Vaasa, Finland.
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Kim, Sung Soo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Minerva Fdn, Helsinki, Finland;Univ Helsinki, Dept Med, Helsinki, Finland;Univ Helsinki, Cent Hosp, Helsinki, Finland.
    Kovacs, Peter
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany.
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia;Univ Tartu, Inst Math Stat, Tartu, Estonia.
    Lange, Leslie A.
    Univ Colorado Denver, Div Bioinformat & Personalized Med, Dept Med, Aurora, CO USA.
    Lee, Jung-Jin
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
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    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lin, Keng-Hung
    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan.
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    Res Ctr Prevent & Hlth, Glostrup, Denmark;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
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    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
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    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Oulu, Inst Hlth Sci, Oulu, Finland;ASTAR, TLGM, Singapore, Singapore.
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    McKean-Cowdin, Roberta
    Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
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    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    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.
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    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Ntalla, Ioanna
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Dusseldorf, Leibniz Ctr Diabet Res Heinrich Heine, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Sch Med, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
    Rode, Line
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Schonherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Selvin, Elizabeth
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Small, Kerrin S.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tin, Adrienne
    Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
    Tonjes, Anke
    Univ Leipzig, Dept Med, Leipzig, Germany.
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
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    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Yajnik, Pranav
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
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    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
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    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
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    Univ Lille Nord France, INSERM, U1167, Inst Pasteur Lille, Lille, France.
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, Nuthetal, Germany.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Collins, Francis S.
    NHGRI, US Natl Inst Hlth, Genome Technol Branch, Bethesda, MD 20892 USA.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Dehghan, Abbas
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;German Ctr Diabet Res DZD, Neuherberg, Germany;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
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    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.
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    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med EPIMED, Varese, Italy.
    Ferrieres, Jean
    INSERM, UMR 1027, Toulouse, France;Toulouse Univ, Sch Med, Dept Cardiol, Toulouse, France.
    Florez, Jose C.
    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Harvard Med Sch, Dept Med, Boston, MA USA.
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    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Harris, Tamara B.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
    Heckbert, Susan R.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kathiresan, Sekar
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth NI, Belfast, Antrim, North Ireland.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany.
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France.
    Morris, Andrew D.
    Ninewells Hosp, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland;Med Sch, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Murray, Alison D.
    Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Biomed Imaging Ctr, Aberdeen, Scotland.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden.
    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.
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Ridker, Paul M.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Rivadineira, Fernando
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Rosengren, Anders H.
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Taichung, Taiwan;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan;Sch Med, Natl Def Med Ctr, Taipei, Taiwan.
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada;Genome Quebec Innovat Ctr, Montreal, PQ, Canada;McGill Univ, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp, Div Populat Hlth Sci, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Uitterlinden, Andre G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
    Willer, Cristen J.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
    Bluher, Matthias
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany;Univ Leipzig, Dept Med, Leipzig, Germany.
    Butterworth, Adam S.
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    van Duijn, Cornelia
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Dupuis, Josee
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany;Ludwig Maximillians Univ Munich, Helmholtz Zentrum Munchen, Clin Cooperat Grp Type Diabet 2, Munich, Germany;Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Helmholtz Zentrum Munchen, Munich, Germany.
    Groop, Leif
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, 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.
    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.
    Kooner, Jaspal Singh
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, Hammersmith Campus, London, England.
    Kottgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Kuulasmaa, Kari
    Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Liu, Yongmei
    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC 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, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Marchini, Jonathan
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Pankow, James S.
    Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Univ Cambridge, Sch Clin Med, Dept Hematol, Cambridge, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Stumvoll, Michael
    Univ Hosp Leipzig, Div Endocrinol, Leipzig, Germany;Univ Hosp Leipzig, Div Nephrol, Leipzig, Germany.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Dasman, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metabol Res Labs, Cambridge, England.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Harvard Med Sch, Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA;Ctr Noncommunicable Dis, Karachi, Pakistan.
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Med,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, 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.
    Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 559-571Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 x 10(-7)); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio <= 1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

  • 154.
    Malik, Rainer
    et al.
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Chauhan, Ganesh
    Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India;Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France.
    Traylor, Matthew
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Okada, Yukinori
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Mishra, Aniket
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Rutten-Jacobs, Loes
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Giese, Anne-Katrin
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA.
    van der Laan, Sander W.
    Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol,Dept Cardiol, Utrecht, Netherlands.
    Gretarsdottir, Solveig
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Anderson, Christopher D.
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Chong, Michael
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Adams, Hieab H. H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands.
    Ago, Tetsuro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Amouyel, Philippe
    Univ Lille, Risk Factors & Mol Determinants Aging Related Dis, Inst Pasteur Lille, INSERM,LabEx DISTALZ,UMR1167, Lille, France;CHU Lille, Epidemiol & Publ Hlth Dept, Lille, France.
    Ay, Hakan
    MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Harvard Med Sch, MGH, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA USA.
    Bartz, Traci M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
    Benavente, Oscar R.
    Univ British Columbia, Brain Res Ctr, Div Neurol, Fac Med, Vancouver, BC, Canada.
    Bevan, Steve
    Univ Lincoln, Sch Life Sci, Lincoln, England.
    Boncoraglio, Giorgio B.
    IRCCS, Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy.
    Brown, Robert D., Jr.
    Mayo Clin, Dept Neurol, Rochester, MN USA.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood, Cambridge, England;Univ Cambridge, Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Carrera, Caty
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Carty, Cara L.
    Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA;George Washington Univ, Ctr Translat Sci, Washington, DC USA.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Chen, Wei-Min
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Cole, John W.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Populat Hlth Sci, Jackson, MS 39216 USA.
    Cotlarciuc, Ioana
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Cruchaga, Carlos
    Washington Univ, Sch Med, Dept Psychiat, Hope Ctr Program Prot Aggregat & Neurodegenerat H, St Louis, MO 63110 USA;Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Cambridge, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
    DeStefano, Anita L.
    Boston Univ, Sch Publ Hlth, Boston, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    den Hoed, Marcel
    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.
    Duan, Qing
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Engelter, Stefan T.
    Basel Univ Hosp, Dept Neurol, Basel, Switzerland;Basel Univ Hosp, Stroke Ctr, Basel, Switzerland;Univ Basel, Neurorehabilitat Unit, Basel, Switzerland;Univ Ctr Med Aging & Rehabil Basel, Felix Platter Hosp, Basel, Switzerland.
    Falcone, Guido J.
    Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA;Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
    Grewal, Raji P.
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc Res Inst, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Haessler, Jeffrey
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Harris, Tamara B.
    NIH, Natl Inst Aging, Lab Epidemiol & Populat Sci, Bldg 10, Bethesda, MD 20892 USA.
    Hassan, Ahamad
    Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Dept Neurol, Leeds, W Yorkshire, England.
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Helsinki, Finland;Inst Mol Med Finland, FIMM, Helsinki, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
    Holliday, Elizabeth G.
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW, Australia;Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia.
    Howard, George
    Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
    Hsu, Fang-Chi
    Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA.
    Hyacinth, Hyacinth I.
    Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorder Ctr, Atlanta, GA USA.
    Ikram, M. Arfan
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    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, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Epidemiol, Birmingham, AL 35294 USA.
    Jian, Xueqiu
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
    Jimenez-Conde, Jordi
    Univ Autonoma Barcelona, Inst Hosp Mar Invest Med, Neurol Dept, Neurovasc Res Grp NEUVAS, Barcelona, Spain.
    Johnson, Julie A.
    Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Kanai, Masahiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Harvard Med Sch, Program Bioinformat & Integrat Gen, Boston, MA USA.
    Keene, Keith L.
    East Carolina Univ, Dept Biol, Greenville, NC USA;East Carolina Univ, Ctr Hlth Dispar, Greenville, NC USA.
    Kissela, Brett M.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kleindorfer, Dawn O.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Kubo, Michiaki
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Lange, Leslie A.
    Univ Colorado Denver, Dept Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    NIH, Natl Inst Aging, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Jin-Moo
    Washington Univ, Sch Med, Dept Neurol Radiol & Biomed Engn, St Louis, MO USA.
    Lemmens, Robin
    Univ Leuven, KU Leuven, Dept Neurosci Expt Neurol, Leuven, Belgium;Univ Hosp Leuven, Dept Neurol, VIB Ctr Brain & Dis Res, Leuven, Belgium.
    Leys, Didier
    Univ Lille, CHU Lille, INSERM, U 1171, Lille, France.
    Lewis, Cathryn M.
    Kings Coll London, Dept Med & Mol Genet, London, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London, England.
    Lin, Wei-Yu
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Newcastle Univ, Northern Inst Canc Res, Newcastle, NSW, Australia.
    Lindgren, Arne G.
    Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden;Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden.
    Lorentzen, Erik
    Univ Gothenburg, Bioinformat Core Facil, Gothenburg, Sweden.
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Maguire, Jane
    Univ Technol Sydney, Fac Hlth, Ultimo, NSW, Australia.
    Manichaikul, Ani
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    McArdle, Patrick F.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Meschia, James F.
    Mayo Clin, Dept Neurol, Jacksonville, FL USA.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA;Baltimore Vet Adm, Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Sch Med, Div Geriatr, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Memory Impairment & Neurodegenerat Dementia Ctr, Jackson, MS 39216 USA.
    Nalls, Michael A.
    NIH, Natl Inst Aging, Lab Neurogenet, Bldg 10, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD USA.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    O'Donnell, Martin J.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Psaty, Bruce M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Pulit, Sara L.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
    Rannikmae, Kristiina
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Reiner, Alexander P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Rexrode, Kathryn M.
    Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Rost, Natalia S.
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA.
    Rothwell, Peter M.
    Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sakaue, Saori
    Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan.
    Sale, Michele M.
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sapkota, Bishwa R.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA.
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Schmidt, Carsten O.
    Univ Med Greifswald, SHIP KEF, Inst Community Med, Greifswald, Germany.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, Greifswald, Germany.
    Sharma, Pankaj
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Slowik, Agnieszka
    Jagiellonian Univ, Dept Neurol, Krakow, Poland.
    Sudlow, Cathie L. M.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Tanislav, Christian
    Justus Liebig Univ, Dept Neurol, Giessen, Germany.
    Tatlisumak, Turgut
    Univ Gothenburg, Sahlgrenska Acad, Inst Neuroscience & Physiol, Dept Clin Neurosci Neurol, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Thijs, Vincent N. S.
    Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Div, Heidelberg, Vic, Australia;Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia.
    Thorleifsson, Gudmar
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Tiedt, Steffen
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, Leiden, Netherlands.
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France.
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands;Ctr Med Syst Biol, Leiden, Netherlands.
    Walters, Matthew
    Univ Glasgow, Sch Med Dent & Nursing, Glasgow, Lanark, Scotland.
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wassertheil-Smoller, Sylvia
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wiggins, Kerri L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Boston, MA USA.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Pastinen, Tomi
    McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
    Ruusalepp, Arno
    Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia;Clin Gene Networks AB, Stockholm, Sweden.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Koplev, Simon
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Bjorkegren, Johan L. M.
    Clin Gene Networks AB, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Univ Tartu, Biomeedikum, Inst Biomedicine & Translat Med, Dept Pathophysiol, Tartu, Estonia;Karolinska Univ Ssjukhuset, Dept Med, Integrated Cardio Metab Ctr, Huddinge, Sweden.
    Codoni, Veronica
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Civelek, Mete
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA;Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
    Smith, Nicholas L.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA;VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
    Tregouet, David A.
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Christophersen, Ingrid E.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Gjettum, Norway.
    Roselli, Carolina
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Lubitz, Steven A.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Ellinor, Patrick T.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Kooner, Jaspal S.
    Imperial Coll London, Natl Heart & Lung Inst, London, England.
    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.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England;Imperial Coll London, NIHR Imperial Biomed Res Ctr, London, England.
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.
    Takeuchi, Fumihiko
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan.
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Natl Heart Lung & Blood Res Inst, Div Intramural Res, Populat Sci Branch, Framingham, MA USA.
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA;Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Jern, Christina
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden.
    Strbian, Daniel
    Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland;Univ Helsinki, Clin Neurosci, Neurol, Helsinki, Finland.
    Fernandez-Cadenas, Israel
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Longstreth, W. T., Jr.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
    Rolfs, Arndt
    Univ Clin Rostock, Albrecht Kossel Inst, Rostock, Germany.
    Hata, Jun
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    Woo, Daniel
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Rosand, Jonathan
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Pare, Guillaume
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
    Stefansson, Kari
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Worrall, Bradford B.
    Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA;Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
    Kittner, Steven J.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Seshadri, Sudha
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA.
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Markus, Hugh S.
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Kamatani, Yoichiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
    Debette, Stephanie
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Dichgans, Martin
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany;Munich Cluster Syst Neurol SyNergy, Munich, Germany;German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
    Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 4, s. 524-537Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

  • 155. Malki, Ninoa
    et al.
    Koupil, Ilona
    Eloranta, Sandra
    Weibull, Caroline E.
    Tiikkaja, Sanna
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sparen, Par
    Temporal Trends in Incidence of Myocardial Infarction and Ischemic Stroke by Socioeconomic Position in Sweden 1987-20102014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e105279-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time. Materials and Methods: We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country. Results: The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2-1.4) in 1997 to 1.5 (1.4-1.7) in 2010 among men, and from 1.4 (1.3-1.6) in 1997 to 2.1 (1.8-2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women. Conclusion: There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

  • 156.
    Marklund, Matti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW 2042, Australia.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Ingelsson, Erik
    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;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Lindgren, Cecilia M.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England;Univ Oxford, Big Data Inst, Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7LF, England.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity2018Inngår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, nr 11, artikkel-id 1791Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of delta-5-desaturase (D5D), delta-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 x 10(-70)) and adipose tissue (p = 1.1 x 10(-27)). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 x 10(-67); PDXDCI, p = 4.8 x 10(-8); and near MC4R, p = 3.7 x 10(-8)) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 x 10(-19)). Genetic variants near MC4R were associated with IS (p = 3.8 x 10(-3)). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.

  • 157.
    Marouli, Eirini
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Medina-Gomez, Carolina
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Lo, Ken Sin
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Kjaer, Troels R.
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    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..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 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 10069 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 10069 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.;Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Rueger, Sina
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Lamparter, David
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Univ Cambridge, Dept Hematol, Cambridge CB2 0PT, England..
    Turcot, Valerie
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany..
    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, EE-51010 Tartu, Estonia..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    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 63108 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA..
    Rivas, Manuel A.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Nuffield Dept Clin Med, Oxford OX3 7BN, England..
    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..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherland Comprehens Canc Org, NL-3501 DB Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Adair, Linda S.
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA..
    Alam, Dewan S.
    Ctr Control Chron Dis, Dhaka 1212, Bangladesh..
    Albrecht, Eva
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Allin, Kristine H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, F-59019 Lille, France.;Inst Pasteur, U1167, F-59019 Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, F-59019 Lille, France..
    Appel, Emil V.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, F-67085 Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, F-67081 Strasbourg, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.;ICIN Netherland 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
    INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France..
    Banas, Bernhard
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark..
    Benn, Marianne
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Bergmann, Sven
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, D-14558 Nuthetal, Germany..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 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 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27157 USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, DK-7100 Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, DK-5000 Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.;NIHR Biomed Res Ctr Mental Hlth Maudsley, London SE5 8AF, England..
    Brilliant, Murray H.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Broer, Linda
    Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Carey, David J.
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA..
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Chambers, John C.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England..
    Chasman, Daniel I.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA..
    Chen, Yii-Der Ida
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Christensen, Cramer
    Lillebaelt Hosp, Dept Med, DK-7100 Vejle, Denmark..
    Chu, Audrey Y.
    Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;NHLBI, Framingham Heart Study, Framingham, MA 01702 USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Collins, Francis S.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.;Univ Cambridge, Dept Med, Cambridge Escellence, British Heart Fdn, Cambridge CB2 0QQ, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    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 Genet, NL-3584 CX Utrecht, Netherlands..
    de Borst, Gert J.
    Univ Med Ctr Utrecht, Dept Vasc Surg, Div Surg Specialties, NL-3584 CX Utrecht, Netherlands..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    de Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, NL-3508 GA Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    den Hollander, Anneke I.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London WC1E 6JF, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Ebeling, Tapani
    Oulu Univ Hosp, Dept Med, Oulu 90029, Finland.;Univ Oulu, Res Unit Internal Med, FI-90014 Oulu, Finland..
    Edwards, Todd L.
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Ellinor, Patrick T.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Evangelou, Evangelos
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Feng, Shuang
    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..
    Ferrario, Marco M.
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, I-21100 Varese, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, F-31059 Toulouse, France..
    Florez, Jose C.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA..
    Ford, Ian
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Frikke-Schmidt, Ruth
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Gandin, Ilaria
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Giri, Ayush
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Girotto, Giorgia
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Gordon, Scott D.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Gordon-Larsen, Penny
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany.;Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 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.
    Hansen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC 27514 USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Univ Exeter Med Sch, Exeter EX2 5DW, Devon, England..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC 27708 USA.;Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Heikkila, Kauko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Dept Cardiol, Ctr Heart, FI-33521 Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7000, Australia..
    Hocking, Lynne J.
    Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh EH4 2XU, Midlothian, Scotland.;Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen AB25 2ZD, Scotland..
    Hollensted, Mette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7600 Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Hoyng, Carel B.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway..
    Ikram, M. Arfan
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Neurol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Radiol, NL-3015 GE Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. 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..
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Res Unit Skelleftea, SE-93141 Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Univ Washington, Dept Genom Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, DK-2000 Frederiksberg, Denmark..
    Jhun, Min A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Jiang, Xuejuan
    Univ Calif Los Angeles, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.;Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Jorgensen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Aalborg Hosp, DK-9000 Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Jukema, J. Wouter
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, NL-2333 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..
    Kahn, Rene S.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland.;Natl Inst Hlth & Welf, FI-00271 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 Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast BT12 6BJ, Antrim, North Ireland..
    Keeman, Renske
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Kluivers, Kirsten B.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kocher, Thomas
    Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodontol, D-17475 Greifswald, Germany..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Kontto, Jukka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London W12 0NN, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Kriebel, Jennifer
    German Ctr Diabet Res, D-85764 Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Kuivaniemi, Helena
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Dept Psychiat, ZA-7505 Tygerberg, Western Cape, South Africa.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, ZA-7505 Tygerberg, Western Cape, South Africa..
    Kury, Sebastien
    CHU Nantes, Serv Genet Med, F-44093 Nantes, France..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    La Bianca, Martina
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Univ Eastern Finland, Inst Biomed & Physiol, Kuopio 70210, Finland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Langefeld, Carl D.
    Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27157 USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA..
    Lee, I-Te
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung 407, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.;Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35205 USA..
    Li, Huaixing
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Li, Jin
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, 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, FI-00271 Helsinki, Finland..
    Linneberg, Allan
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.;Rigshosp, Dept Expt Med, DK-2200 Copenhagen, Denmark..
    Liu, Yeheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA..
    Lophatananon, Artitaya
    Warsaw Acad Med & Hosp, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Lubitz, Steven A.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Mackey, David A.
    Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia..
    Madden, Pamela A. F.
    Washington Univ, Dept Psychiat, St Louis, MO 63110 USA..
    Manning, Alisa K.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Meidtner, Karina
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW 2022, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW 2022, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands..
    Morgan, Anna
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Morris, Andrew D.
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Univ Munich, Dept Med 1, D-81377 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem, D-17475 Greifswald, Germany.;Univ Med Greifswald, Lab Med, D-17475 Greifswald, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Nikus, Kjell
    Univ Tampere, Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.;Univ Tampere, Sch Med, Tampere 33521, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Ntalla, Ioanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Oksa, Heikki
    Tampere Univ Hosp, Dept Med, Tampere 33521, Finland..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Ophoff, Roel A.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee DD1 9SY, Scotland..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, NL-3584 CX Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Peloso, Gina M.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Perola, Markus
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, FI-00014 Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Perry, James A.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Person, Thomas N.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Split, Sch Med, Split 21000, Croatia..
    Posthuma, Danielle
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogenom & Cognit Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Reilly, Dermot F.
    MRL Merck & Co Inc, Genet & Pharmacogenom, Boston, MA 02115 USA..
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Renstrom, Frida
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Umea Univ, Dept Biobank Res, SE-90187 Umea, Sweden..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA..
    Rioux, John D.
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England..
    Robino, Antonietta
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Saleheen, Danish
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Sandow, Kevin
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Schmidt, Marjanka K.
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Schreiner, Pamela J.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    Schulze, Matthias B.
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Segura-Lepe, Marcelo P.
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Shah, Svati
    Duke Univ, Durham, NC 27703 USA..
    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..
    Sivapalaratnam, Suthesh
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.;AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Smith, Albert Vernon
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 Kopavogur, Iceland..
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Southam, Lorraine
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, 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 EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    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, D-04103 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    't Hart, Leen M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol & Cell Biol, NL-2333 ZC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Tansey, Katherine E.
    Cardiff Univ, Coll Biomed & Life Sci, Cardiff CF14 4EP, S Glam, Wales.;Univ Bristol, Dept Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Teumer, Alexander
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.;Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, D-04103 Leipzig, Germany..
    Tromp, Gerard
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Human Genet & Mol Biol, ZA-7505 Tygerberg, Western Cape, South Africa..
    Trompet, Stella
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.;Dasman Diabet Inst, Dasman 15462, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 4R2, Canada..
    Uitterlinden, Andre G.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ulivi, Sheila
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands..
    Van Der Leij, Andries R.
    Univ Amsterdam, Dept Brain & Cognit, NL-1018 WS Amsterdam, Netherlands..
    van Duijn, Cornelia M.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands..
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Vogt, Thomas F.
    MRL Merck Co Inc, Cardiometab Dis, Kenilworth, NJ 07033 USA..
    Vozzi, Diego
    Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Wang, Feijie
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Wang, Yiqin
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Warren, Helen R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Wessel, Jennifer
    Indiana Univ, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Dept Epidemiol & Med, Indianapolis, IN 46202 USA.;Indiana Univ, Sch Med, Indianapolis, IN 46202 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, DK-5000 Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark..
    Woods, Michael O.
    Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Yao, Pang
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA.;GlaxoSmithKlein, King Of Prussia, PA 19406 USA..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dept Clin Sci, Dallas, TX 75390 USA..
    Zhang, Weihua
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, 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 19104 USA..
    Zheng, He
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    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..
    Stefansson, Kari
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA 17033 USA..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC 27514 USA.;Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA..
    Heard-Costa, Nancy L.
    NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Pers, Tune H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, DK-2200 Copenhagen, Denmark..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England..
    Oxvig, Claus
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Rivadeneira, Fernando
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    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 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Hirschhorn, Joel N.
    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.;Harvard Med Sch, Dept Pediat & Genet, Boston, MA 02115 USA..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia..
    Lettre, Guillaume
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Rare and low-frequency coding variants alter human adult height2017Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, nr 7640, s. 186-190Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

  • 158. McManus, David D
    et al.
    Lyass, Asya
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Massaro, Joseph M
    Meigs, James B
    Aragam, Jayashri
    Benjamin, Emelia J
    Vasan, Ramachandran S
    Relations of circulating resistin and adiponectin and cardiac structure and function: the Framingham Offspring Study.2012Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 20, nr 9, s. 1882-1886Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obesity is associated with pathological cardiac remodeling and risk of heart failure (HF). Adipocytokines (ADKs) may mediate the increased risk of cardiovascular disease associated with excess adiposity. Yet data relating ADKs to cardiac remodeling phenotypes are sparse. We related two circulating ADKs, resistin and adiponectin, to three important echocardiographic markers of cardiac remodeling, left ventricular mass (LVM), left atrial diameter (LAD), and LV fractional shortening (LVFS) in 2,615 participants (mean age 61 years, 55% women) in the Framingham Offspring Study. Adiponectin concentrations were inversely related to LVM in multivariable linear regression models adjusting for key clinical correlates including BMI (regression coefficient per s.d.-increment in ln-adiponectin = -3.37, P = 0.02; P for trend across quartiles = 0.02). Adiponectin was not associated with LAD or LVFS (P > 0.56). Resistin concentrations were inversely related to LVFS (regression coefficient per s.d.-increment in ln-resistin = -0.01, P = 0.03; P for trend across quartiles = 0.04). Resistin was not associated with LVM or LAD (P > 0.05). In our moderate-sized, community-based sample, higher circulating concentrations of adiponectin and resistin were associated with lower LVM and lower LVFS, respectively. In conclusion, these associations identify potential mechanisms by which excess adiposity may mediate adverse cardiac remodeling and HF risk.

  • 159.
    Mendelson, Michael M.
    et al.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Joehanes, Roby
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA..
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Boston Univ, Dept Biostat, Boston, MA USA..
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Guan, Weihua
    Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA..
    Zhi, Degui
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA..
    Yao, Chen
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Huan, Tianxiao
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Willinger, Christine
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Chen, Brian
    NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Courchesne, Paul
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Multhaup, Michael
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Lrvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Cohain, Ariella
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Bressler, Jan
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    North, Kari
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Shah, Sonia
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    McRae, Allan F.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland..
    Gibson, Jude
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Redmond, Paul
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Coriey, Janie
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Murphy, Lee
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland..
    Kleinbrink, Erica
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Lipovich, Leonard
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Visscher, Peter M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Wray, Naomi R.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Krauss, Ronald M.
    Childrens Hosp Oakland Res Inst, Oakland, CA USA..
    Fallin, Daniele
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Feinberg, Andrew
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Absher, Devin M.
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ Texas Houston, Brown Fdn Inst Mol Med, Houston, TX USA..
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fox, Caroline
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 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..
    Arnett, Donna K.
    Univ Kentucky, Coll Publ Hlth, Lexington, KY USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Liang, Liming
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Deary, Lan J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach2017Inngår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, nr 1, artikkel-id e1002215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

  • 160. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Gaulton, Kyle J
    Nadkarni, Girish N
    Valladares-Salgado, Adan
    Wacher-Rodarte, Niels
    Mychaleckyj, Josyf C
    Dueker, Nicole D
    Guo, Xiuqing
    Hai, Yang
    Haessler, Jeffrey
    Kamatani, Yoichiro
    Stilp, Adrienne M
    Zhu, Gu
    Cook, James P
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Blanton, Susan H
    de Borst, Martin H
    Bottinger, Erwin P
    Buchanan, Thomas A
    Cechova, Sylvia
    Charchar, Fadi J
    Chu, Pei-Lun
    Damman, Jeffrey
    Eales, James
    Gharavi, Ali G
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Heath, Andrew C
    Ipp, Eli
    Kiryluk, Krzysztof
    Kramer, Holly J
    Kubo, Michiaki
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lindgren, Cecilia M
    Lu, Yingchang
    Madden, Pamela A F
    Montgomery, Grant W
    Papanicolaou, George J
    Raffel, Leslie J
    Sacco, Ralph L
    Sanchez, Elena
    Stark, Holger
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Taylor, Kent D
    Xiang, Anny H
    Zivkovic, Aleksandra
    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. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, Stanford Univ, Stanford Cardiovasc Inst, Stanford, USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, USA.
    Martin, Nicholas G
    Whitfield, John B
    Cai, Jianwen
    Laurie, Cathy C
    Okada, Yukinori
    Matsuda, Koichi
    Kooperberg, Charles
    Chen, Yii-Der Ida
    Rundek, Tatjana
    Rich, Stephen S
    Loos, Ruth J F
    Parra, Esteban J
    Cruz, Miguel
    Rotter, Jerome I
    Snieder, Harold
    Tomaszewski, Maciej
    Humphreys, Benjamin D
    Franceschini, Nora
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, nr 1, artikkel-id 29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 161.
    Mubanga, Mwenya
    et al.
    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.
    Egenvall, Agneta
    Swedish Univ Agr Sci, Div Ruminant Med & Vet Epidemiol, Dept Clin Sci, Uppsala, Sweden.
    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, 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.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dog Ownership and Survival After a Major Cardiovascular Event: A Register-Based Prospective Study2019Inngår i: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 12, nr 10, artikkel-id e005342Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Dog ownership is associated with increased physical activity levels and increased social support, both of which could improve the outcome after a major cardiovascular event. Dog ownership may be particularly important in single-occupancy households where ownership provides substitutive companionship and motivation for physical activity.

    Methods and Results: We used the Swedish National Patient Register to identify all patients aged 40 to 85 presenting with an acute myocardial infarction (n=181 696; 5.7% dog ownership) or ischemic stroke (n=154 617; 4.8% dog ownership) between January 1, 2001 and December 31, 2012. Individual information was linked across registers for cause of death, sociodemographic, and dog ownership data. We evaluated all-cause mortality and risk of recurrent hospitalization for the same cause until December 31, 2012. Models were adjusted for socioeconomic, health, and demographic factors at study inclusion such as age, marital status, the presence of children in the home, area of residence, and income, as well as all registered comorbidities and hospitalization for cardiovascular disease in the past 5 years. Dog owners had a lower risk of death after hospitalization for acute myocardial infarction during the full follow-up period of 804 137 person-years, with an adjusted hazard ratio (HR) of 0.67 (95% CI, 0.61 to 0.75) for those who lived alone, and HR of 0.85 (95% CI, 0.80 to 0.90) for those living with a partner or a child. Similarly, after an ischemic stroke, dog owners were at lower risk of death during the full follow-up of 638 219 person-years adjusted HR of 0.73 (95% CI, 0.66 to 0.80) for those who lived alone and HR of 0.88 (95% CI, 0.83 to 0.93) for those living with a partner or a child. We further found an association of dog ownership with reduced risk of hospitalization for recurrent myocardial infarction (HR, 0.93; 95% CI, 0.87 to 0.99).

    Conclusions: We found evidence of an association of dog ownership with a better outcome after a major cardiovascular event. Although our models are adjusted for many potential confounders, there are also unmeasured confounders such as smoking that prevent us from drawing conclusions regarding a possible causal effect.

  • 162.
    Mubanga, Mwenya
    et al.
    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.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study2019Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, artikkel-id e023447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To study the association between dog ownership and cardiovascular risk factors.

    Design A nationwide register–based cohort study and a cross-sectional study in a subset.

    Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

    Participants All Swedish residents aged 45–80 years on 1 October, 2006.

    Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

    Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

    Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

  • 163.
    Mubanga, Mwenya
    et al.
    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.
    Nowak, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dog ownership and the risk of cardiovascular disease and death: a nationwide cohort study2017Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, nr 1, artikkel-id 15821Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65-0.69) and 0.89 (0.87-0.91), respectively; and CVD death, HR 0.64 (0.59-0.70), and 0.85 (0.81-0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89-0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.

  • 164. Nagy, Edit
    et al.
    Eriksson, Per
    Yousry, Mohamed
    Caidahl, Kenneth
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Hansson, Göran K
    Franco-Cereceda, Anders
    Bäck, Magnus
    Valvular osteoclasts in calcification and aortic valve stenosis severity2013Inngår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, nr 3, s. 2264-2271Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Bone remodeling in calcified aortic valves is thought to originate from microfractures at multiple sites of the valve, at which osteoclasts and osteoblasts are recruited. The aim of the present study was to assess circulating mediators of bone homeostasis, correlate them to the severity of stenosis and explore the spatio-temporal distribution of bone turnover in different parts of calcified aortic valve tissue.

    METHODS AND RESULTS: Plasma and explanted aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery. Plasma levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear-κB (RANK) ligand and Runt-related transcription factor 2 (Runx2/Cbfa1) exhibited a significant correlation to the severity of aortic stenosis. mRNA levels in normal, thickened and calcified parts of aortic valves assessed by quantitative real-time PCR were significantly elevated in calcified parts of valves for TRAP (5.08 ± 1.6-fold, P<0.001) RANK ligand (8.6 ± 4.2-fold, P<0.001) and RANK (1.98 ± 0.78-fold, P=0.015). In an age, gender and aortic valve anatomy-adjusted multivariable regression analysis the local transcript levels of TRAP correlated significantly with echocardiographic parameters quantifying stenosis severity in early stages, whereas the expression level of Runx2/Cbfa1 was a predictor of the stenosis severity in advanced stages.

    CONCLUSIONS: These findings suggest a critical role of bone turnover as a determinant of aortic stenosis severity.

  • 165. Nelson, C. P.
    et al.
    Hamby, S. E.
    Saleheen, D.
    Hopewell, J. C.
    Zeng, L.
    Assimes, T. L.
    Kanoni, S.
    Willenborg, C.
    Burgess, S.
    Amouyel, P.
    Anand, S.
    Blankenberg, S.
    Boehm, B. O.
    Clarke, R. J.
    Collins, R.
    Dedoussis, G.
    Farrall, M.
    Franks, P. W.
    Groop, L.
    Hall, A. S.
    Hamsten, A.
    Hengstenberg, C.
    Hovingh, G. Kees
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kathiresan, S.
    Kee, F.
    Koenig, I. R.
    Kooner, J.
    Lehtimaeki, T.
    Maerz, W.
    McPherson, R.
    Metspalu, A.
    Nieminen, M. S.
    O'Donnell, C. J.
    Palmer, C. N. A.
    Peters, A.
    Perola, M.
    Reilly, M. P.
    Ripatti, S.
    Roberts, R.
    Salomaa, V.
    Shah, S. H.
    Schreiber, S.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Thorsteinsdottir, U.
    Veronesi, G.
    Wareham, N.
    Willer, C. J.
    Zalloua, P. A.
    Erdmann, J.
    Deloukas, P.
    Watkins, H.
    Schunkert, H.
    Danesh, J.
    Thompson, J. R.
    Samani, N. J.
    Genetically Determined Height and Coronary Artery Disease2015Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 372, nr 17, s. 1608-1618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quar-tile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association.

  • 166.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Jobs, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    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 folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 11, s. 2069-2074Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 167. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jobs, Magnus
    Larsson, Anders
    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.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 8, s. 1550-1555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 168.
    Nettleton, Jennifer A.
    et al.
    Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA..
    Follis, Jack L.
    Univ St Thomas, Dept Math, Houston, TX 77006 USA..
    Ngwa, Julius S.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Smith, Caren E.
    Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA.;Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Ahmad, Shafqat
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Tanaka, Toshiko
    NIA, Clin Res Branch, Baltimore, MD 21224 USA..
    Wojczynski, Mary K.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Voortman, Trudy
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Kristiansson, Kati
    Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland..
    Nuotio, Marja-Liisa
    Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland..
    Houston, Denise K.
    Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA..
    Perala, Mia-Maria
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland..
    Qi, Qibin
    Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Albert Einstein Coll Med, Dept Epidemiol & Publ Hlth, Bronx, NY 10467 USA..
    Sonestedt, Emily
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.;Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Ganna, Andrea
    Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Mikkila, Vera
    Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    North, Kari E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.;Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Siscovick, David S.
    New York Acad Med, New York, NY USA..
    Harald, Kennet
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Mckeown, Nicola M.
    Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA.;Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Johansson, Ingegerd
    Umea Univ, Dept Odontol, Umea, Sweden..
    Rissanen, Harri
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA..
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Hu, Frank B.
    Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Bandinelli, Stefania
    ASF, Geriatr Unit, Florence, Italy..
    Rukh, Gull
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Rich, Stephen
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA..
    Booij, Lisanne
    NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Dmitriou, Maria
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Ax, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.;Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland..
    Mukamal, Kenneth
    Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland..
    Hallmans, Goran
    Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden..
    Jula, Antti
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Ericson, Ulrika
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Jacobs, David R., Jr.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Van Rooij, Frank J. A.
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Deloukas, Panos
    Wellcome Trust Sanger Inst, Hinxton, Cambs, England..
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Djousse, Luc
    Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA.;Boston VA Healthcare Syst, Boston, MA USA..
    Perola, Markus
    Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, Cambs, England.;Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England..
    Hofman, Albert
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Stirrups, Kathleen
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Viikari, Jorma
    Univ Turku, Dept Med, Turku, Finland.;Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland..
    Uitterlinden, Andre G.
    NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Kalafati, Ioanna P.
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Franco, Oscar H.
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Salomaa, Veikko
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Knekt, Paul
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Kritchevsky, Stephen B.
    Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA..
    Eriksson, Johan G.
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland.;Univ Helsinki, Inst Clin Med, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland..
    Dedoussis, George V.
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Qi, Lu
    Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Ferrucci, Luigi
    NIA, Clin Res Branch, Baltimore, MD 21224 USA..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Zillikens, M. Carola
    NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lehtimaki, Terho
    Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland.;Univ Tampere, Sch Med, FIN-33101 Tampere, Finland..
    Renstrom, Frida
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, 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..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Gene x dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry2015Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 16, s. 4728-4738Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

  • 169. Nettleton, Jennifer A.
    et al.
    Hivert, Marie-France
    Lemaitre, Rozenn N.
    McKeown, Nicola M.
    Mozaffarian, Dariush
    Tanaka, Toshiko
    Wojczynski, Mary K.
    Hruby, Adela
    Djousse, Luc
    Ngwa, Julius S.
    Follis, Jack L.
    Dimitriou, Maria
    Ganna, Andrea
    Houston, Denise K.
    Kanoni, Stavroula
    Mikkila, Vera
    Manichaikul, Ani
    Ntalla, Ioanna
    Renstrom, Frida
    Sonestedt, Emily
    van Rooij, Frank J. A.
    Bandinelli, Stefania
    de Koning, Lawrence
    Ericson, Ulrika
    Hassanali, Neelam
    Kiefte-de Jong, Jessica C.
    Lohman, Kurt K.
    Raitakari, Olli
    Papoutsakis, Constantina
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Stirrups, Kathleen
    Ax, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Deloukas, Panos
    Groves, Christopher J.
    Jacques, Paul F.
    Johansson, Ingegerd
    Liu, Yongmei
    McCarthy, Mark I.
    North, Kari
    Viikari, Jorma
    Zillikens, M. Carola
    Dupuis, Josee
    Hofman, Albert
    Kolovou, Genovefa
    Mukamal, Kenneth
    Prokopenko, Inga
    Rolandsson, Olov
    Seppala, Ilkka
    Cupples, L. Adrienne
    Hu, Frank B.
    Kahonen, Mika
    Uitterlinden, Andre G.
    Borecki, Ingrid B.
    Ferrucci, Luigi
    Jacobs, David R., Jr.
    Kritchevsky, Stephen B.
    Orho-Melander, Marju
    Pankow, James S.
    Lehtimaki, Terho
    Witteman, Jacqueline C. M.
    Ingelsson, Erik
    Siscovick, David S.
    Dedoussis, George
    Meigs, James B.
    Franks, Paul W.
    Meta-Analysis Investigating Associations Between Healthy Diet and Fasting Glucose and Insulin Levels and Modification by Loci Associated With Glucose Homeostasis in Data From 15 Cohorts2013Inngår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 177, nr 2, s. 103-115Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG ( 0.004 mmol/L, 95 confidence interval: 0.005, 0.003) and FI ( 0.008 ln-pmol/L, 95 confidence interval: 0.009, 0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions.

  • 170.
    Ng, Esther
    et al.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. Uppsala Univ, Dept Med Sci Occupat & Environm Med, S-75185 Uppsala, Sweden..
    Lindgren, Cecilia
    Harvard Univ, Inst Technol, Broad Inst Massachusetts, Cambridge, MA 02142 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Morris, Andrew
    Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Genome-wide association study of toxic metals and trace elements reveals novel associations2015Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 16, s. 4739-4745Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The accumulation of toxic metals in the human body is influenced by exposure and mechanisms involved in metabolism, some of which may be under genetic control. This is the first genome-wide association study to investigate variants associated with whole blood levels of a range of toxic metals. Eleven toxic metals and trace elements (aluminium, cadmium, cobalt, copper, chromium, mercury, manganese, molybdenum, nickel, lead and zinc) were assayed in a cohort of 949 individuals using mass spectrometry. DNA samples were genotyped on the Infinium Omni Express bead microarray and imputed up to reference panels from the 1000 Genomes Project. Analyses revealed two regions associated with manganese level at genome-wide significance, mapping to 4q24 and 1q41. The lead single nucleotide polymorphism(SNP) in the 4q24 locus was rs13107325 (P-value = 5.1 x 10(-11), beta = -0.77), located in an exon of SLC39A8, which encodes a protein involved in manganese and zinc transport. The lead SNP in the 1q41 locus is rs1776029 (P-value = 2.2 x 10(-14), beta = -0.46). The SNP lies within the intronic region of SLC30A10, another transporter protein. Among other metals, the loci 6q14.1 and 3q26.32 were associated with cadmium and mercury levels (P = 1.4x10(-10), beta = -1.2 and P = 1.8x10(-9), beta = -1.8, respectively). Whole blood measurements of toxicmetals are associated with genetic variants in metal transporter genes and others. This is relevant in inferring metabolic pathways of metals and identifying subsets of individuals who may be more susceptible to metal toxicity.

  • 171. Ng, Esther
    et al.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Mahajan, Anubha
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindgren, Cecilia M
    van Bavel, Bert
    Morris, Andrew P
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample2015Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 140, s. 95-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level.

    OBJECTIVES: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.

    METHODS: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography-high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model.

    RESULTS: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10(-13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10(-12)) for PCB-118, rs4802104 (p=1.4×10(-9)) for PCB-74 and rs4803413 (p=2.5×10(-9)) for PCB-105, all of which map to CYP2B6.

    CONCLUSIONS: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity.

  • 172.
    Nielsen, Jonas B.
    et al.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Fritsche, Lars G.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Zhou, Wei
    Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Teslovich, Tanya M.
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;St Olavs Univ Hosp, Dept Cardiol, N-7030 Trondheim, Norway..
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Gabrielsen, Maiken E.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Schmidt, Ellen M.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Beaumont, Robin
    Royal Devon & Exeter NHS Fdn Trust, Exeter EX2 5WD, Devon, England.;Univ Exeter, Exeter EX2 5WD, Devon, England..
    Wolford, Brooke N.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Lin, Maoxuan
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Brummett, Chad M.
    Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA..
    Preuss, Michael H.
    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..
    Refsgaard, Lena
    Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark..
    Bottinger, Erwin P.
    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..
    Graham, Sarah E.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Surakka, Ida
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Chu, Yunhan
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Skogholt, Anne Heidi
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Dalen, Havard
    St Olavs Univ Hosp, Dept Cardiol, N-7030 Trondheim, Norway.;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, N-7491 Trondheim, Norway..
    Boyle, Alan P.
    Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Oral, Hakan
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Herron, Todd J.
    Univ Michigan, Ctr Arrhythmia Res, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Kitzman, Jacob
    Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Jalife, Jose
    Univ Michigan, Ctr Arrhythmia Res, Dept Internal Med, Ann Arbor, MI 48109 USA.;Fdn Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain..
    Svendsen, Jesper H.
    Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark..
    Olesen, Morten S.
    Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Dept Biomed, DK-2200 Copenhagen, Denmark..
    Njolstad, Inger
    UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway..
    Lochen, Maja-Lisa
    UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway..
    Baras, Aris
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Gottesman, Omri
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Marcketta, Anthony
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    O'Dushlaine, Colm
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Ritchie, Marylyn D.
    Geisinger Hlth Syst, Danville, PA 17822 USA..
    Wilsgaard, Tom
    UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway..
    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..
    Frayling, Timothy M.
    Royal Devon & Exeter NHS Fdn Trust, Exeter EX2 5WD, Devon, England.;Univ Exeter, Exeter EX2 5WD, Devon, England..
    Boehnke, Michael
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Division of Cardiovascular Medicine, Depart- ment of Medicine, Stanford University School of Medicine, Stanford, USA.
    Carey, David J.
    Dewey, Frederick E.
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Kang, Hyun M.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Abecasis, Goncalo R.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, N-7600 Levanger, Norway..
    Willer, Cristen J.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development2018Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 102, nr 1, s. 103-115Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.

  • 173.
    Nikpay, Majid
    et al.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Goel, Anuj
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Won, Hong-Hee
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    Hall, Leanne M.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England..
    Willenborg, Christina
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Kyriakou, Theodosios
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Webb, Thomas R.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Zeng, Lingyao
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Armasu, Sebastian M.
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA..
    Auro, Kirsi
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Bjonnes, Andrew
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Chen, Shufeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA..
    Gieger, Christian
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;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..
    Grace, Christopher
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Huang, Jie
    Wellcome Trust Sanger Inst, Hinxton, England..
    Hwang, Shih-Jen
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Kim, Yun Kyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany..
    Lau, King Wai
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Lu, Xiangfeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Lu, Yingchang
    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..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Qu, Liming
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Salfati, Elias
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Saxena, Richa
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA..
    Scholz, Markus
    Univ Leipzig, Fac Med, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.;LIFE Res Ctr Civilizat Dis, Leipzig, Germany..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Tikkanen, Emmi
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Uitterlinden, Andre
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Yang, Xueli
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England..
    Zhao, Wei
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA..
    de Andrade, Mariza
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA..
    de Vries, Paul S.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    van Zuydam, Natalie R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Dundee, Med Res Inst, Dundee, Scotland..
    Anand, Sonia S.
    McMaster Univ, Dept Med, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada..
    Bertram, Lars
    Univ Lubeck, Inst Neurogenet & Integrat, Platform Genome Analyt, Lubeck, Germany.;Univ Lubeck, Inst Expt Gen, Platform Genome Analyt, Lubeck, Germany.;Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Neuroepidemiol & Ageing Res Unit, London, England..
    Beutner, Frank
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Leipzig, Heart Ctr Leipzig, Cardiol, D-04109 Leipzig, Germany..
    Dedoussis, George
    Harokopio Univ, Dept Dietet Nutr, Athens, Greece..
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Gauguier, Dominique
    INSERM, Ctr Rech Cordeliers, UMRS 1138, Paris, France..
    Goodall, Alison H.
    Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Haber, Marc
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Huang, Jianfeng
    Peking Union Med Coll, Beijing 100021, Peoples R China.;Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Hypertens Div, Beijing 100730, Peoples R China..
    Jalilzadeh, Shapour
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kessler, Thorsten
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;Klinikum Rechts Der Isar, Munich, Germany..
    Koenig, Inke R.
    DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany.;Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol, Kiel, Germany..
    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 MIT & Harvard Univ, Cambridge, MA USA..
    Lokki, Marja-Liisa
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Mallick, Nadeem H.
    Punjab Inst Cardiol, Lahore, Pakistan..
    Mehra, Narinder
    All India Inst Med Sci, New Delhi, India..
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Humangenet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany..
    Memon, Fazal-ur-Rehman
    Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Nieminen, Markku S.
    Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Rallidis, Loukianos S.
    Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, GR-11527 Athens, Greece..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan..
    Samuel, Maria
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Shah, Svati H.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Wang, Laiyuan
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China.;Natl Human Genome Ctr Beijing, Beijing, Peoples R China..
    Zaman, Khan S.
    Natl Inst Cardiovasc Dis, Karachi, Pakistan..
    Ardissino, Diego
    Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy.;Assoc Studio Trombosi Cardiol, Pavia, Italy..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Buring, Julie E.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Chambers, John C.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Collins, Rory
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Cupples, L. Adrienne
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Demuth, Ilja
    Berlin Aging Study 2, Berlin, Germany.;Charite, Res Grp Geriatr, D-13353 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Elosua, Roberto
    Inst Hosp Mar Invest Med IMIM, Grp Epidemiol & Genet Cardiovasc, Barcelona, Spain..
    Epstein, Stephen E.
    MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, Washington, DC USA..
    Esko, Tonu
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol & Basic & Translat Obes Res, Boston, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Franzosi, Maria Grazia
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy..
    Granger, Christopher B.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Gu, Dongfeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Hall, Alistair S.
    Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Hazen, Stanley L.
    Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA..
    Hengstenberg, Christian
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    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, England.;Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Iribarren, Carlos
    Kaiser Permanente Div Res, Oakland, CA USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands..
    Karhunen, Pekka J.
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Forens Med, FIN-33101 Tampere, Finland..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Kooner, Jaspal S.
    Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Kullo, Iftikhar J.
    Mayo Clin, Dept Med, Cardiovasc Dis, Rochester, MN USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland..
    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..
    Melander, Olle
    Lund Univ, Univ Hosp Malmo, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany.;Synlab Acad, Synlab Serv, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Palmer, Colin N.
    Univ Dundee, Med Res Inst, Dundee, Scotland..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Quertermous, Thomas
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Roberts, Robert
    Univ Ottawa, Inst Heart, Ottawa, ON, Canada..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Coll Med, Oklahoma City, OK 73190 USA.;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA.;Oklahoma Ctr Neurosci, Oklahoma City, OK USA..
    Schwartz, Stephen M.
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Seedorf, Udo
    Univ Med Ctr Hamburg Eppendorf, Ctr Dent & Oral Med, Dept Prosthet Dent, Hamburg, Germany..
    Stewart, Alexandre F.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Stott, David J.
    Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Thiery, Joachim
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Hosp Leipzig, Fac Med, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany..
    Zalloua, Pierre A.
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA..
    O'Donnell, Christopher J.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.;Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA..
    Reilly, Muredach P.
    Assimes, Themistocles L.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Thompson, John R.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany..
    Clarke, Robert
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Watkins, Hugh
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    McPherson, Ruth
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia..
    Schunkert, Heribert
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Farrall, Martin
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 10, s. 1121-1130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

  • 174.
    Nolte, Ilja M.
    et al.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Munoz, M. Loretto
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Amare, Azmeraw T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands.;Univ Adelaide, Sch Med, Dept Epidemiol, Adelaide, SA 5005, Australia.;Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar 6000, Ethiopia..
    Jansen, Rick
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands.;Isfahan Univ Med Sci, Sch Med, Esfahan 8174673461, Iran..
    von der Heyde, Benedikt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Avery, Christy L.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA..
    Dierckx, Bram
    Dept Child & Adolescent Psychiat, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Erasmus MC, Generat Study Grp R, POB 2060, NL-3000 CB0 Rotterdam, Netherlands..
    van Dongen, Jenny
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands..
    Gogarten, Stephanie M.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Goyette, Philippe
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere 33521, Finland..
    Huikari, Ville
    Univ Oulu, Ctr Life Course Hlth Res, Oulu 90014, Finland..
    Hwang, Shih-Jen
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Jaju, Deepali
    Sultan Qaboos Univ Hosp, Dept Clin Physiol, Muscat 123, Oman..
    Kerr, Kathleen F.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Kluttig, Alexander
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol Biostat & Informat, D-06097 Halle, Germany..
    Krijthe, Bouwe P.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Kumar, Jitender
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Dept Heart & Lung, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Maihofer, Adam X.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    Minassian, Arpi
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Dept Med, Univ Hosp Munich, D-80539 Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany..
    Nivard, Michel
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Salvi, Erika
    Univ Milan, Dept Hlth Sci, I-20122 Milan, Italy..
    Stewart, James D.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.;Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA..
    Thayer, Julian F.
    Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Wong, Andrew
    UCL, MRC Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England..
    Zabaneh, Delilah
    Kings Coll London, Inst Psychiat Psychol & Neurosci, De Crespigny Pk, London SE5 8AF, England.;UCL, Genet Inst, London WC1E 6BT, England..
    Zafarmand, Mohammad H.
    Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynaecol, NL-1105 AZ Amsterdam, Netherlands..
    Abdellaoui, Abdel
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Albarwani, Sulayma
    Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Physiol, Muscat Al Khoudh 123, Oman..
    Albert, Christine
    Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA..
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA..
    Ashar, Foram
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA..
    Auvinen, Juha
    Univ Oulu, Ctr Life Course Hlth Res, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu 90220, Finland..
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Baker, Dewleen G.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Dept Genet, Ctr Mol Med, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands..
    Barcella, Matteo
    Univ Milan, Dept Hlth Sci, I-20122 Milan, Italy..
    Bayoumi, Riad
    Mohammed Bin Rashid Univ, Coll Med, Dubai Healthcare City, POB 505055, Dubai, U Arab Emirates..
    Bieringa, Rob J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Boomsma, Dorret
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Boucher, Gabrielle
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada..
    Britton, Annie R.
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England..
    Christophersen, Ingrid E.
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA.;MIT, Cambridge, MA 02114 USA.;Baerum Hosp, Vestre Viken Hosp Trust, Dept Med Res, N-1346 Rud, Norway..
    Dietrich, Andrea
    Univ Groningen, Univ Med Ctr Groningen, Dept Child & Adolescent Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Ehret, George B.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA.;Geneva Univ Hosp, Dept Specialties Internal Med, Cardiol, CH-1211 Geneva, Switzerland..
    Ellinor, Patrick T.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA.;MIT, Cambridge, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Eskola, Markku
    Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Cardiol, Tampere 33014, Finland..
    Felix, Janine F.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Floras, John S.
    Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.;Univ Toronto, Mt Sinai Hosp, Div Cardiol, Dept Med, Toronto, ON, Canada.;Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON M5G 2C4, Canada..
    Franco, Oscar H.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Friberg, Peter
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, Dept Mol & Clin Med, SE-41345 Gothenburg, Sweden..
    Gademan, Maaike G. J.
    Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands..
    Geyer, Mark A.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Dept Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Hemerich, Daiane
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil..
    Hofman, Albert
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Huikuri, Heikki
    Oulu Univ Hosp, Med Res Ctr, Res Unit Internal Med, Oulu 90220, Finland.;Univ Oulu, SF-90220 Oulu, Finland..
    Hutri-Kahonen, Nina
    Tampere Univ Hosp, Dept Pediat, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Pediat, Tampere 33014, Finland..
    Jouven, Xavier
    Paris Descartes Univ, INSERM, U970, F-75006 Paris, France..
    Junttila, Juhani
    Oulu Univ Hosp, Med Res Ctr, Res Unit Internal Med, Oulu 90220, Finland.;Univ Oulu, SF-90220 Oulu, Finland..
    Juonala, Markus
    Univ Turku, Dept Med, Turku 20520, Finland.;Turku Univ Hosp, Div Med, Turku 20521, Finland..
    Kiviniemi, Antti M.
    Oulu Univ Hosp, Med Res Ctr, Res Unit Internal Med, Oulu 90220, Finland.;Univ Oulu, SF-90220 Oulu, Finland..
    Kors, Jan A.
    Erasmus MC, Dept Med Informat, NL-3015 CE Rotterdam, Netherlands..
    Kumari, Meena
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.;Essex Univ, ISER, Colchester CO4 3SQ, Essex, England..
    Kuznetsova, Tatiana
    Univ Leuven, KU Leuven Dept Cardiovasc Sci, Studies Coordinating Ctr, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Leuven, Belgium..
    Laurie, Cathy C.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Lefrandt, Joop D.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Vasc Med, POB 30001, NL-9700 RB Groningen, Netherlands..
    Li, Yong
    Univ Freiburg, Fac Med, Med Center, Div Genet Epidemiol,Inst Med Biometry & Stat, D-79110 Freiburg, Germany..
    Li, Yun
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA..
    Liao, Duanping
    Penn State Univ, Coll Med, Dept Publ Hlth Sci, Div Epidemiol, Hershey, PA 17033 USA..
    Limacher, Marian C.
    Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA..
    Lin, Henry J.
    Harbor UCLA Med Ctr, Dept Pediat, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Div Med Genet, Torrance, CA 90502 USA..
    Lindgren, Cecilia M.
    Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Lubitz, Steven A.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA.;MIT, Cambridge, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    McKnight, Barbara
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA.;Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA..
    zu Schwabedissen, Henriette Meyer
    Univ Basel, Dept Pharmaceut Sci, Biopharm, CH-4056 Basel, Switzerland..
    Milaneschi, Yuri
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Mononen, Nina
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA..
    Navis, Gerjan
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Neijts, Melanie
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Nikus, Kjell
    Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Cardiol, Tampere 33014, Finland..
    North, Kari E.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.;Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA..
    O'Connor, Daniel T.
    Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA..
    Ormel, Johan
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Dept Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Perz, Siegfried
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Peters, Annette
    Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;German Ctr Diabet Res, D-85764 Neuherberg, Germany..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA.;Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland..
    Risbrough, Victoria B.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    Sinner, Moritz F.
    Ludwig Maximilians Univ Munchen, Dept Med, Univ Hosp Munich, D-80539 Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany..
    Siscovick, David
    New York Acad Med, New York, NY 10029 USA..
    Smit, Johannes H.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Smith, Nicholas L.
    Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.;Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA..
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Div Publ Hlth Sci, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27157 USA..
    Sotoodehnia, Nona
    Univ Washington, Dept Med & Epidemiol, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA..
    Staessen, Jan A.
    Univ Leuven, KU Leuven Dept Cardiovasc Sci, Studies Coordinating Ctr, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Leuven, Belgium..
    Stein, Phyllis K.
    Washington Univ, Heart Rate Variabil Lab, Sch Med, St Louis, MO 63108 USA..
    Stilp, Adrienne M.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Stolarz-Skrzypek, Katarzyna
    Jagiellonian Univ, Med Coll, Dept Cardiol Intervent Electrocardi & Hypertens 1, PL-31008 Krakow, Poland..
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany..
    Sundstrom, Johan
    Uppsala Univ, Dept Med Sci Cardiovasc Epidemiol, S-75185 Uppsala, Sweden..
    Swenne, Cees A.
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands..
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada.;Univ Montreal, Montreal, PQ H3T IJ4, Canada..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat & Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thornton, Timothy A.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Tinker, Lesley E.
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA..
    Uitterlinden, Andre G.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Internal Med, NL-3015 CE Rotterdam, Netherlands.;Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, NL-2300 RC Leiden, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Voss, Andreas
    IGHT Jena Ernst Abbe Hsch, Inst Innovat Hlth Technol, D-07745 Jena, Germany..
    Waldenberger, Melanie
    Dept Child & Adolescent Psychiat, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Wilhelmsen, Kirk C.
    Univ N Carolina, Dept Genet & Neurol, Chapel Hill, NC 27599 USA.;Renaissance Comp Inst, Chapel Hill, NC 27599 USA..
    Willemsen, Gonneke
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Wong, Quenna
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Zhang, Zhu-Ming
    Wake Forest Sch Med, Div Publ Hlth Sci, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Cusi, Daniele
    Italian Natl Res Council, CNR, Inst Biomed Technol, I-20090 Milan, Italy.;KOS Genet SRL, I-20091 Milan, Italy..
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Greiser, Halina K.
    German Canc Res Ctr, Div Canc Epidemiol, D-69210 Heidelberg, Germany..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Hassan, Mohammad
    Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Physiol, Muscat Al Khoudh 123, Oman..
    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, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA..
    Jarvelin, Marjo-Riitta
    Univ Oulu, Ctr Life Course Hlth Res, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu 90220, Finland.;Imperial Coll London, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, St Marys Campus, London, England.;Univ Oulu, Bioctr Oulu, Oulu 90014, Finland..
    Kaab, Stefan
    Ludwig Maximilians Univ Munchen, Dept Med, Univ Hosp Munich, D-80539 Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA..
    Kuh, Diana
    UCL, MRC Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Lind, Lars
    Uppsala Univ, Dept Med Sci Cardiovasc Epidemiol, S-75185 Uppsala, Sweden..
    Nievergelt, Caroline M.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    O'Donnell, Chris J.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Boston Vet Adm Healthcare Boston, Cardiol Sect, Boston, MD 02132 USA..
    Oldehinkel, Albertine J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Dept Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Penninx, Brenda
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Reiner, Alexander P.
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA.;Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA..
    Riese, Harriette
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Dept Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    van Roon, Arie M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Vasc Med, POB 30001, NL-9700 RB Groningen, Netherlands..
    Rioux, John D.
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada.;Univ Montreal, Montreal, PQ H3T IJ4, Canada..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat & Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Sofer, Tamar
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Stricker, Bruno H.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Inspectorate Hlth Care, NL-2511 VX The Hague, Netherlands..
    Tiemeier, Henning
    Dept Child & Adolescent Psychiat, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Vrijkotte, Tanja G. M.
    Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-3501 DG Utrecht, Netherlands..
    Brundel, Bianca J. J. M.
    Vrije Univ Amsterdam, Inst Cardiovasc Res, Dept Physiol, Med Ctr, De Boelelaan 1118, NL-1081 HV Amsterdam, Netherlands..
    Heckbert, Susan R.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA.;Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA..
    Whitsel, Eric A.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA..
    den Hoed, Marcel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    de Geus, Eco J. C.
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Genetic loci associated with heart rate variability and their effects on cardiac disease risk2017Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, artikkel-id 15805Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.

  • 175.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Hetty, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Castillejo-Lopez, Casimiro
    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, Stockholm, Sweden.
    Cook, Naomi L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Shen, Xia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    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, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 8691Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

  • 176.
    Nowak, Christoph
    et al.
    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.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Use of type 2 diabetes risk scores in clinical practice: a call for action2015Inngår i: LANCET DIABETES & ENDOCRINOLOGY, ISSN 2213-8587, Vol. 3, nr 3, s. 166-167Artikkel i tidsskrift (Annet vitenskapelig)
  • 177.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    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 USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.;Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Brandmaier, Stefan
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
    Tukiainen, Taru
    Univ Helsinki, FIMM, Helsinki, Finland..
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Wang-Sattler, Rui
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Gieger, Christian
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Ripatti, Samuli
    Univ Helsinki, FIMM, Helsinki, Finland.;Univ Helsinki, Fac Med, Publ Hlth, Helsinki, Finland.;Wellcome Trust Sanger Inst, Hinxton, 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 MEB, Stockholm, Sweden..
    Sundström, Johan
    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 Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study2016Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, nr 10, artikkel-id e1006379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

  • 178.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundstrom, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Type 2 diabetes, glycaemic traits and cardiovascular disease: a Mendelian Randomization studyManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Type 2 diabetes (T2D) and its hallmarks insulin resistance, impaired insulin secretion, and hyperglycaemia affect over 400 million persons worldwide and are associated with raised cardiovascular risk, but their causal role has been difficult to dissect due to overlap between risk factors. We used Mendelian randomization analysis, which utilises genetic polymorphisms associated with a risk factor, to assess causal effects of T2D, insulin resistance, insulin secretion, and fasting glucose on mortality, ischaemic stroke, and coronary artery disease (CAD) risk in 120,091 adults in the UK Biobank and in the CARDIoGRAMplusC4D consortium (63,746 cases of CAD and 130,681 controls). We found evidence for a causal effect of T2D on raised CAD risk (odds ratio (OR) per doubling in the odds of T2D, 1.07, 95% confidence interval (CI) 1.05 – 1.09, P = 1.2 x 10-9) and for a causal effect of impaired insulin secretion on the risk of CAD (OR per SD-unit decrease, 1.14, 95% CI 1.06 – 1.22, P = 0.002). The genetic score for insulin resistance was associated with increased coronary artery disease risk; however, sensitivity analysis indicated that the instrument might not be appropriate to use for robust causal inference testing. Our results support previous reports of a causal role of T2D and impaired insulin secretion in coronary artery disease and point to a complex relationship between variants affecting insulin resistance and cardiovascular outcomes.

  • 179.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Sundstrom, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ganna, Andrea
    Massachusetts General Hospital, Harvard Medical School and Broad Institute, Boston, Massachusetts.
    Shen, Xia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm , Sweden.
    Broeckling, Corey D.
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, USA.
    Prenni, Jessica
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, USA.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. School of Health and Social Studies, Dalarna University, Falun, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
    Metabolite profiles during an oral glucose tolerance test reveal new associations with clamp-measured insulin sensitivityManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Impaired insulin sensitivity (IS) is a major risk factor for cardiovascular disease and type 2 diabetes. Metabolomic profiling during an oral glucose tolerance test (OGTT) can reveal early pathogenic alterations in healthy individuals. Our aim was to identify IS biomarkers and gain new pathophysiologic insights by applying untargeted metabolomics to repeated OGTT plasma samples in association with a hyperinsulinemic-euglycemic clamp assessment. We studied 192 metabolites identified by non-targeted liquid chromatography/mass spectrometry in plasma samples taken at 0, 30, and 120 min during an OGTT in 470 non-diabetic 71-yr-old men. Insulin sensitivity was associated with 35 metabolites at one or more time points in multivariable-adjusted linear regression. The trajectories of nine metabolites during the OGTT were related to IS, six of which (oleic and palmitoleic acid, decanoyl- and dodecanoylcarnitine, deoxycholate-glycine and hexose) showed no associations with IS in the baseline fasting state. The strongest effects were detected for medium-chain acylcarnitines, which increased between 30-120 min in insulin-resistant individuals compared to those with normal IS. In this large community sample, we identified novel associations between clamp-measured IS and metabolite profiles that became apparent only after an oral glucose challenge. Associations of differential medium-chain acylcarnitine and monounsaturated fatty acid trajectories with IS provide new insights into the pathogenesis of insulin resistance.

  • 180.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    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.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large Community Cohorts2016Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, nr 1, s. 276-284Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved risk prediction and understanding of the pathogenesis are needed. We used a novel high-throughput 92-protein assay to identify circulating biomarkers for HOMA of IR in two cohorts of community residents without diabetes (n = 1,367) (mean age 73 ± 3.6 years). Adjusted linear regression identified cathepsin D and confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid-binding protein 4, and tissue plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers, IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03-1.59) and t-PA (HR 1.30, 1.02-1.65) were associated with incident T2D, and t-PA predicted 5-year transition to hyperglycemia (odds ratio 1.30, 95% CI 1.02-1.65). Additional adjustment for fasting glucose rendered both coefficients insignificant and revealed an association between renin and T2D (HR 0.79, 0.62-0.99). LASSO regression suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study T2D score, but prediction improvement was nonsignificant (difference in C-index 0.02, 95% CI -0.08 to 0.12) over the T2D score only. In conclusion, proteomic blood profiling indicated cathepsin D as a new IR biomarker and suggested a causal effect of IR on t-PA.

  • 181. Parikh, Nisha I
    et al.
    Cnattingius, Sven
    Dickman, Paul W
    Mittleman, Murray A
    Ludvigsson, Jonas F
    Ingelsson, Erik
    Karolinska Institutet, Stockholm, Sweden.
    Parity and risk of later-life maternal cardiovascular disease2010Inngår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 159, nr 2, s. 215-221.e6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Prior studies relating parity with maternal cardiovascular disease (CVD) have been performed in relatively small study samples without accounting for pregnancy-related complications associated with CVD.

    METHODS: We examined the associations between parity and maternal risk of later-life CVD in a population-based cohort study using data from the Swedish population registers. Women born from 1932 to 1955 were followed until the occurrence of CVD, death, emigration, or end of follow-up (December 31, 2005). Cox proportional hazards models were used to estimate associations between parity and risk of CVD accounting for birth year, yearly income, education level, country of birth, hypertension (pregestational hypertension or gestational hypertension, with or without proteinuria), diabetes (type 1, type 2, or gestational diabetes), preterm birth, small for gestational age, and stillbirth.

    RESULTS: During a median follow-up time of 9.5 years (range 0-23.5), there were 65,204 CVD events in the full sample of women. Among 1,332,062 women, parity was associated with CVD in a J-shaped fashion, with 2 births representing the nadir of risk (global P value < .0001). Upon accounting for pregnancy-related complications in a subset of women with at least 1 childbirth after 1973 (n = 590,725), the association of parity with CVD was similar. Compared with women with 2 childbirths, the multivariable-adjusted hazard ratios (95% CIs) for women with 1 and >/=5 births were 1.09 (1.03-1.15) and 1.47 (1.37-1.57), respectively.

    CONCLUSIONS: In conclusion, parity was associated with incident maternal CVD in a J-shaped fashion, even after accounting for socioeconomic factors and pregnancy-related complications.

  • 182. Parikh, Nisha I
    et al.
    Cnattingius, Sven
    Mittleman, Murray A
    Ludvigsson, Jonas F
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Subfertility and risk of later life maternal cardiovascular disease2012Inngår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 27, nr 2, s. 568-575Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Subfertility shares common pathways with cardiovascular disease (CVD), including polycystic ovarian syndrome, obesity and thyroid disorders. Women with prior 0-1 pregnancies are at an increased risk of incident CVD when compared with women with two pregnancies. It is uncertain whether history of subfertility among women eventually giving birth is a risk factor for CVD.

    METHODS: Among Swedish women with self-reported data on subfertility in the Swedish Medical Birth Register (n = 863 324), we used Cox proportional hazards models to relate a history of subfertility to CVD risk after adjustment for age, birth year, highest income, education, birth country, hypertension, diabetes, preterm birth, small for gestational age (SGA), smoking and for BMI in separate models. In additional analyses, we excluded women with: (i) pregnancy-related or non-pregnancy-related hypertension and/or diabetes; and (ii) preterm births and/or SGA babies.

    RESULTS: Among nulliparous women eventually having a childbirth (between 1983 and 2005, the median follow-up time 11.9; 0-23 years and 9 906 621 person-years of follow-up), there was an increased risk of CVD among women reporting ≥ 5 years of subfertility versus 0 years (hazard ratio 1.19, 95% confidence interval 1.02-1.39). There were not significantly elevated CVD risks for women with 1-2 or 3-4 years of subfertility versus 0 years. Accounting for BMI did not change results. Excluding women with hypertension and/or diabetes attenuated associations, whereas exclusion of women with preterm and/or SGA births did not change findings.

    CONCLUSIONS: Subfertility among women eventually having a childbirth is a risk factor for CVD even upon accounting for cardiovascular risk factors and adverse pregnancy outcomes. Future studies should explore the mechanisms underlying this association.

  • 183.
    Parikh, Nisha I.
    et al.
    Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA..
    Norberg, Margareta
    Umea Univ, Dept Publ Hlth & Clin Med, Epidemiol & Global Hlth, S-90187 Umea, Sweden..
    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, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Cnattingius, Sven
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Vasan, Ramachandran S.
    Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02215 USA.;Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA..
    Domellof, Magnus
    Umea Univ, Pediat Unit, Dept Clin Sci, S-90187 Umea, Sweden..
    Jansson, Jan Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit Skelleftea, S-90187 Umea, Sweden..
    Bonamy, Anna-Karin Edstedt
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens Childrens Hlth, Stockholm, Sweden..
    Association of Pregnancy Complications and Characteristics With Future Risk of Elevated Blood Pressure The Västerbotten Intervention Program2017Inngår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 69, nr 3, s. 475-483Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pregnancy characteristics are associated with risk of cardiovascular diseases, but their independent associations with hypertension or blood pressure (BP) levels remain uncertain. We linked the Swedish Medical Birth Register with Vesterbotten Intervention Program data (Northern Sweden). Using linear and logistic regression, we related pregnancy factors in any prior pregnancy with BP and hypertension at 40 years of age in 15 896 parous women free of prepregnancy hypertension. Pregnancy factors included parity, age at first delivery, preeclampsia, gestational diabetes mellitus, placental abruption, shortest gestational age small for gestational age baby (<third percentile for birth weight) or stillbirth. We defined hypertension as systolic BP >= 140 mm Hg and diastolic BP >= 90 mm Hg or antihypertensive use. Multivariable models were adjusted for all pregnancy factors and potential lifestyle and sociodemographic confounders. At 40 years of age, 1535 women (9.6%) had hypertension. In multivariable models, lower parity, younger age at first birth, preeclampsia, small for gestational age, and placental abruption were independently associated with higher systolic and diastolic BP levels at 40 years of age. Younger age at first birth, preeclampsia, gestational age <32 versus >= 37 weeks, and small for gestational age were independently associated with hypertension. Our findings raise the possibility that earlier and more frequent BP screening may be desirable in women with these pregnancy characteristics.

  • 184.
    Penell, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Morris, Andrew P
    Lindgren, Cecilia
    Mahajan, Anubha
    Salihovic, Samira
    van Bavel, Bert
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, P Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Genetic variation in the CYP2B6 Gene is related to circulating 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) concentrations: an observational population-based study2014Inngår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, s. 34-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample.

    METHODS:

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS).

    RESULTS:

    Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10-4 to 10-9). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals.

    CONCLUSION:

    Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.

  • 185. Perry, John R. B.
    et al.
    Day, Felix
    Elks, Cathy E.
    Sulem, Patrick
    Thompson, Deborah J.
    Ferreira, Teresa
    He, Chunyan
    Chasman, Daniel I.
    Esko, Toenu
    Thorleifsson, Gudmar
    Albrecht, Eva
    Ang, Wei Q.
    Corre, Tanguy
    Cousminer, Diana L.
    Feenstra, Bjarke
    Franceschini, Nora
    Ganna, Andrea
    Johnson, Andrew D.
    Kjellqvist, Sanela
    Lunetta, Kathryn L.
    McMahon, George
    Nolte, Ilja M.
    Paternoster, Lavinia
    Porcu, Eleonora
    Smith, Albert V.
    Stolk, Lisette
    Teumer, Alexander
    Tsernikova, Natalia
    Tikkanen, Emmi
    Ulivi, Sheila
    Wagner, Erin K.
    Amin, Najaf
    Bierut, Laura J.
    Byrne, Enda M.
    Hottenga, Jouke-Jan
    Koller, Daniel L.
    Mangino, Massimo
    Pers, Tune H.
    Yerges-Armstrong, Laura M.
    Zhao, Jing Hua
    Andrulis, Irene L.
    Anton-Culver, Hoda
    Atsma, Femke
    Bandinelli, Stefania
    Beckmann, Matthias W.
    Benitez, Javier
    Blomqvist, Carl
    Bojesen, Stig E.
    Bolla, Manjeet K.
    Bonanni, Bernardo
    Brauch, Hiltrud
    Brenner, Hermann
    Buring, Julie E.
    Chang-Claude, Jenny
    Chanock, Stephen
    Chen, Jinhui
    Chenevix-Trench, Georgia
    Collee, J. Margriet
    Couch, Fergus J.
    Couper, David
    Coviello, Andrea D.
    Cox, Angela
    Czene, Kamila
    D'adamo, Adamo Pio
    Smith, George Davey
    De Vivo, Immaculata
    Demerath, Ellen W.
    Dennis, Joe
    Devilee, Peter
    Dieffenbach, Aida K.
    Dunning, Alison M.
    Eiriksdottir, Gudny
    Eriksson, Johan G.
    Fasching, Peter A.
    Ferrucci, Luigi
    Flesch-Janys, Dieter
    Flyger, Henrik
    Foroud, Tatiana
    Franke, Lude
    Garcia, Melissa E.
    Garcia-Closas, Montserrat
    Geller, Frank
    de Geus, Eco E. J.
    Giles, Graham G.
    Gudbjartsson, Daniel F.
    Gudnason, Vilmundur
    Guenel, Pascal
    Guo, Suiqun
    Hall, Per
    Hamann, Ute
    Haring, Robin
    Hartman, Catharina A.
    Heath, AndrewC.
    Hofman, Albert
    Hooning, Maartje J.
    Hopper, John L.
    Hu, Frank B.
    Hunter, David J.
    Karasik, David
    Kiel, Douglas P.
    Knight, Julia A.
    Kosma, Veli-Matti
    Kutalik, Zoltan
    Lai, Sandra
    Lambrechts, Diether
    Lindblom, Annika
    Maegi, Reedik
    Magnusson, Patrik K.
    Mannermaa, Arto
    Martin, Nicholas G.
    Masson, Gisli
    McArdle, Patrick F.
    McArdle, Wendy L.
    Melbye, Mads
    Michailidou, Kyriaki
    Mihailov, Evelin
    Milani, Lili
    Milne, Roger L.
    Nevanlinna, Heli
    Neven, Patrick
    Nohr, Ellen A.
    Oldehinkel, Albertine J.
    Oostra, Ben A.
    Palotie, Aarno
    Peacock, Munro
    Pedersen, Nancy L.
    Peterlongo, Paolo
    Peto, Julian
    Pharoah, Paul D. P.
    Postma, Dirkje S.
    Pouta, Anneli
    Pylkaes, Katri
    Radice, Paolo
    Ring, Susan
    Rivadeneira, Fernando
    Robino, Antonietta
    Rose, Lynda M.
    Rudolph, Anja
    Salomaa, Veikko
    Sanna, Serena
    Schlessinger, David
    Schmidt, Marjanka K.
    Southey, Mellissa C.
    Sovio, Ulla
    Stampfer, Meir J.
    Stoeckl, Doris
    Storniolo, Anna M.
    Timpson, Nicholas J.
    Tyrer, Jonathan
    Visser, Jenny A.
    Vollenweider, Peter
    Voelzke, Henry
    Waeber, Gerard
    Waldenberger, Melanie
    Wallaschofski, Henri
    Wang, Qin
    Willemsen, Gonneke
    Winqvist, Robert
    Wolffenbuttel, Bruce H. R.
    Wright, Margaret J.
    Boomsma, Dorret I.
    Econs, Michael J.
    Khaw, Kay-Tee
    Loos, Ruth J. F.
    McCarthy, Mark I.
    Montgomery, Grant W.
    Rice, John P.
    Streeten, Elizabeth A.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Alizadeh, Behrooz Z.
    Bergmann, Sven
    Boerwinkle, Eric
    Boyd, Heather A.
    Crisponi, Laura
    Gasparini, Paolo
    Gieger, Christian
    Harris, Tamara B.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jaervelin, Marjo-Riitta
    Kraft, Peter
    Lawlor, Debbie
    Metspalu, Andres
    Pennell, Craig E.
    Ridker, Paul M.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Tim D.
    Strachan, David P.
    Uitterlinden, Andre G.
    Wareham, Nicholas J.
    Widen, Elisabeth
    Zygmunt, Marek
    Murray, Anna
    Easton, Douglas F.
    Stefansson, Kari
    Murabito, Joanne M.
    Ong, Ken K.
    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche2014Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 514, nr 7520, s. 92-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-causemortality(1). Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation(2,3), but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

  • 186. Perry, John R. B.
    et al.
    Hsu, Yi-Hsiang
    Chasman, Daniel I.
    Johnson, Andrew D.
    Elks, Cathy
    Albrecht, Eva
    Andrulis, Irene L.
    Beesley, Jonathan
    Berenson, Gerald S.
    Bergmann, Sven
    Bojesen, Stig E.
    Bolla, Manjeet K.
    Brown, Judith
    Buring, Julie E.
    Campbell, Harry
    Chang-Claude, Jenny
    Chenevix-Trench, Georgia
    Corre, Tanguy
    Couch, Fergus J.
    Cox, Angela
    Czene, Kamila
    D'adamo, Adamo Pio
    Davies, Gail
    Deary, Ian J.
    Dennis, Joe
    Easton, Douglas F.
    Engelhardt, Ellen G.
    Eriksson, Johan G.
    Esko, Tonu
    Fasching, Peter A.
    Figueroa, Jonine D.
    Flyger, Henrik
    Fraser, Abigail
    Garcia-Closas, Montse
    Gasparini, Paolo
    Gieger, Christian
    Giles, Graham
    Guenel, Pascal
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hall, Per
    Hayward, Caroline
    Hopper, John
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Kardia, L. R.
    Kasiman, Katherine
    Knight, Julia A.
    Lahti, Jari
    Lawlor, Debbie A.
    Magnusson, Patrik K. E.
    Margolin, Sara
    Marsh, Julie A.
    Metspalu, Andres
    Olson, Janet E.
    Pennell, Craig E.
    Polasek, Ozren
    Rahman, Iffat
    Ridker, Paul M.
    Robino, Antonietta
    Rudan, Igor
    Rudolph, Anja
    Salumets, Andres
    Schmidt, Marjanka K.
    Schoemaker, Minouk J.
    Smith, Erin N.
    Smith, Jennifer A.
    Southey, Melissa
    Stoeckl, Doris
    Swerdlow, Anthony J.
    Thompson, Deborah J.
    Truong, Therese
    Ulivi, Sheila
    Waldenberger, Melanie
    Wang, Qin
    Wild, Sarah
    Wilson, James F.
    Wright, Alan F.
    Zgaga, Lina
    Ong, Ken K.
    Murabito, Joanne M.
    Karasik, David
    Murray, Anna
    DNA mismatch repair gene MSH6 implicated in determining age at natural menopause2014Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, nr 9, s. 2490-2497Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to 50 of the variation in both age at menarche and menopause, but to date the known genes explain 15 of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P 1.9 10(9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.

  • 187.
    Persson, Jonas
    et al.
    Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Karolinska Inst, S-18288 Danderyd, Sweden..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    McLeod, Olga
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.;Karolinska Inst, Div Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden..
    Silveira, Angela
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Baldassarre, Damiano
    Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy..
    Van Zuydam, Natalie
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 4HN, Scotland..
    Shah, Sonia
    UCL, Genet Inst, London, England.;Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia..
    Fava, Cristiano
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Res Ctr, Malmo, Sweden.;Univ Verona, Hosp Policlin GB Rossi, Dept Med, Div Internal Med C, I-37100 Verona, Italy..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Veglia, Fabrizio
    Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy..
    Sennblad, Bengt
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.;Karolinska Inst, Sci Life Lab, Stockholm, Sweden..
    Larsson, Malin
    Linkoping Univ, IFM Bioinformat, Linkoping, Sweden..
    Sabater-Lleal, Maria
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Leander, Karin
    Gigante, Bruna
    Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Karolinska Inst, S-18288 Danderyd, Sweden.;Karolinska Inst, Div Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden..
    Tabak, Adam
    Semmelweis Univ, Fac Med, Dept Med 1, H-1085 Budapest, Hungary..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Smit, Andries J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-9700 AB Groningen, Netherlands..
    Mannarino, Elmo
    Univ Perugia, Dept Clin & Expt Med, Internal Med Angiol & Arteriosclerosis Dis, I-06100 Perugia, Italy..
    Giral, Philippe
    Grp Hosp Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, F-75634 Paris, France..
    Humphries, Steve E.
    UCL, Ctr Cardiovasc Genet, London, England..
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy..
    de Faire, Ulf
    Karolinska Inst, Div Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden..
    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.
    Hedblad, Bo
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Res Ctr, Malmo, Sweden..
    Melander, Olle
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Clin Res Ctr, Malmo, Sweden..
    Kumari, Meena
    UCL, Genet Epidemiol Grp, Dept Epidemiol & Publ Hlth, London, England..
    Hingorani, Aroon
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.;UCL, Genet Epidemiol Grp, Dept Epidemiol & Publ Hlth, London, England..
    Morris, Andrew D.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 4HN, Scotland..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 4HN, Scotland..
    Lundman, Pia
    Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Karolinska Inst, S-18288 Danderyd, Sweden..
    Ohrvik, John
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden..
    Soderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Div Med, S-90187 Umea, Sweden..
    Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease2015Inngår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, nr 8, artikkel-id e001853Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background-Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results-Baseline plasma adiponectin concentrationwas tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (beta=-0.018, P<0.001) in men but not in women (beta=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (beta=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82,95% CI0.54 to 1.25). Agenescore of adiponectin-raisingalleles in6loci, reported recently inalarge multi-ethnic metaanalysis, was inversely associated with baseline mean bifurcation IMT in men (beta=-0.0008, P=0.004) but not in women (beta=-0.0003, P=0.522; P for interaction=0.007). Conclusions-This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.

  • 188. Prokopenko, Inga
    et al.
    Poon, Wenny
    Mägi, Reedik
    Prasad B, Rashmi
    Salehi, S Albert
    Almgren, Peter
    Osmark, Peter
    Bouatia-Naji, Nabila
    Wierup, Nils
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Stančáková, Alena
    Barker, Adam
    Lagou, Vasiliki
    Osmond, Clive
    Xie, Weijia
    Lahti, Jari
    Jackson, Anne U
    Cheng, Yu-Ching
    Liu, Jie
    O'Connell, Jeffrey R
    Blomstedt, Paul A
    Fadista, Joao
    Alkayyali, Sami
    Dayeh, Tasnim
    Ahlqvist, Emma
    Taneera, Jalal
    Lecoeur, Cecile
    Kumar, Ashish
    Hansson, Ola
    Hansson, Karin
    Voight, Benjamin F
    Kang, Hyun Min
    Levy-Marchal, Claire
    Vatin, Vincent
    Palotie, Aarno
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mari, Andrea
    Weedon, Michael N
    Loos, Ruth J F
    Ong, Ken K
    Nilsson, Peter
    Isomaa, Bo
    Tuomi, Tiinamaija
    Wareham, Nicholas J
    Stumvoll, Michael
    Widen, Elisabeth
    Lakka, Timo A
    Langenberg, Claudia
    Tönjes, Anke
    Rauramaa, Rainer
    Kuusisto, Johanna
    Frayling, Timothy M
    Froguel, Philippe
    Walker, Mark
    Eriksson, Johan G
    Ling, Charlotte
    Kovacs, Peter
    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, England.
    McCarthy, Mark I
    Shuldiner, Alan R
    Silver, Kristi D
    Laakso, Markku
    Groop, Leif
    Lyssenko, Valeriya
    A Central Role for GRB10 in Regulation of Islet Function in Man2014Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, nr 4, artikkel-id e1004235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.

  • 189. Pulit, Sara L.
    et al.
    Gustafsson, Stefan
    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, Klinisk epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Sheth, Kevin
    Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes2018Inngår i: NEUROLOGY-GENETICS, ISSN 2376-7839, Vol. 4, nr 6, artikkel-id e293Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. Methods We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. Results We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Conclusions Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

  • 190.
    Quertermous, Thomas
    et al.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Cardiovasc Inst, Sch Med, Stanford, CA 94305 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, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA..
    Coronary Artery Disease and Its Risk Factors Leveraging Shared Genetics to Discover Novel Biology2016Inngår i: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 118, nr 1, s. 14-16Artikkel i tidsskrift (Annet vitenskapelig)
  • 191. Rahman, Iffat
    et al.
    Humphreys, Keith
    Bennet, Anna Michaela
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Pedersen, Nancy Lee
    Magnusson, Patrik Karl Erik
    Clinical depression, antidepressant use and risk of future cardiovascular disease2013Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, nr 7, s. 589-595Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many studies have shown that depression contributes to a higher risk of developing cardiovascular disease (CVD). Use of antidepressants and its association with CVD development has also been investigated previously but the results have been conflicting. Further, depression and use of antidepressants have been more widely studied in relation to coronary heart disease rather than stroke. A population-based cohort study consisting of 36,654 Swedish elderly twins was conducted with a follow-up of maximum 4 years. Information on exposures, outcomes and covariates were collected from the Swedish national patient registers, the Swedish prescribed drug registry and the Swedish twin registry. Depression and antidepressant use were both associated with CVD development. The risk was most pronounced among depressed patients who did not use antidepressants (HR 1. 48, CI 1.10-2.00). When assessing the two main CVD outcomes coronary heart disease and ischemic stroke separately, the predominant association was found for ischemic stroke while it was absent for coronary heart disease. The association between depression and stroke also remained significant when restricting to depression diagnoses occurring at least 10 years before baseline. The study supports that depression is a possible risk factor for development of CVD. Moreover, the hazard rate for CVD outcomes was highest among depressed patients who had not used antidepressants. The association with clinical depression is more marked in relation to stroke and disappears in relation to development of coronary heart disease.

  • 192. Reynolds, Chandra A
    et al.
    Zavala, Catalina
    Gatz, Margaret
    Vie, Loryana
    Johansson, Boo
    Malmberg, Bo
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Prince, Jonathan A
    Pedersen, Nancy L
    Sortilin receptor 1 predicts longitudinal cognitive change2013Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, nr 6, s. 1710.e11-1710.e18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women.

  • 193. Rietveld, Cornelius A.
    et al.
    Medland, Sarah E.
    Derringer, Jaime
    Yang, Jian
    Esko, Tonu
    Martin, Nicolas W.
    Westra, Harm-Jan
    Shakhbazov, Konstantin
    Abdellaoui, Abdel
    Agrawal, Arpana
    Albrecht, Eva
    Alizadeh, Behrooz Z.
    Amin, Najaf
    Bamard, John
    Baumeister, Sebastian E.
    Benke, Kelly S.
    Bielak, Lawrence F.
    Boatman, Jeffrey A.
    Boyle, Patricia A.
    Davies, Gail
    De Leeuw, Christiaan
    Eklund, Niina
    Evans, Daniel S.
    Ferhmann, Rudolf
    Fischer, Krista
    Gieger, Christian
    Gjessing, Hakon K.
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Harris, Jennifer R.
    Hayward, Caroline
    Holzapfel, Christina
    Ibrahim-Verbaas, Carla A.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jacobsson, Bo
    Joshi, Peter K.
    Jugessur, Astanand
    Kaakinen, Marika
    Kanoni, Stavroula
    Karjalainen, Juha
    Kolcic, Ivana
    Kristiansson, Kati
    Kutalik, Zoltan
    Lahti, Jari
    Lee, Sang H.
    Lin, Peng
    Lind, Penelope A.
    Liu, Yongmei
    Lohman, Kurt
    Loitfelder, Marisa
    McMahon, George
    Vidal, Pedro Marques
    Meirelles, Osorio
    Milani, Lili
    Myhre, Ronny
    Nuotio, Marja-Liisa
    Oldmeadow, Christopher J.
    Petrovic, Katja E.
    Peyrot, Wouter J.
    Polasek, Ozren
    Quaye, Lydia
    Reinmaa, Eva
    Rice, John P.
    Rizzi, Thais S.
    Schmidt, Helena
    Schmidt, Reinhold
    Smith, Albert V.
    Smith, Jennifer A.
    Tanaka, Toshiko
    Terracciano, Antonio
    van der Loos, Matthijs J. H. M.
    Vitart, Veronique
    Voelzke, Henry
    Wellmann, Juergen
    Yu, Lei
    Zhao, Wei
    Allik, Jueri
    Attia, John R.
    Bandinelli, Stefania
    Bastardot, Franois
    Beauchamp, Jonathan
    Bennett, David A.
    Berger, Klaus
    Bierut, Laura J.
    Boomsma, Dorret I.
    Bueltmann, Ute
    Campbell, Harry
    Chabris, Christopher F.
    Cherkas, Lynn
    Chung, Mina K.
    Cucca, Francesco
    de Andrade, Mariza
    De Jager, Philip L.
    De Neve, Jan-Emmanuel
    Deary, Ian J.
    Dedoussis, George V.
    Deloukas, Panos
    Dimitriou, Maria
    Eiriksdottir, Guony
    Elderson, Martin F.
    Eriksson, Johan G.
    Evans, David M.
    Faul, Jessica D.
    Ferrucci, Luigi
    Garcia, Melissa E.
    Groenberg, Henrik
    Guonason, Vilmundur
    Hall, Per
    Harris, Juliette M.
    Harris, Tamara B.
    Hastie, Nicholas D.
    Heath, Andrew C.
    Hernandez, Dena G.
    Hoffmann, Wolfgang
    Hofman, Adriaan
    Holle, Rolf
    Holliday, Elizabeth G.
    Hottenga, Jouke-Jan
    Iacono, William G.
    Illig, Thomas
    Jaervelin, Marjo-Riitta
    Kaehoenen, Mika
    Kaprio, Jaakko
    Kirkpatrick, Robert M.
    Kowgier, Matthew
    Latvala, Antti
    Launer, Lenore J.
    Lawlor, Debbie A.
    Lehtimaeki, Terho
    Li, Jingmei
    Lichtenstein, Paul
    Lichtner, Peter
    Liewald, David C.
    Madden, Pamela A.
    Magnusson, Patrik K. E.
    Maekinen, Tomi E.
    Masala, Marco
    McGue, Matt
    Metspalu, Andres
    Mielck, Andreas
    Miller, Michael B.
    Montgomery, Grant W.
    Mukherjee, Sutapa
    Nyholt, Dale R.
    Oostra, Ben A.
    Palmer, Lyle J.
    Palotie, Aarno
    Penninx, Brenda W. J. H.
    Perola, Markus
    Peyser, Patricia A.
    Preisig, Martin
    Raeikkoenen, Katri
    Raitakari, Olli T.
    Realo, Anu
    Ring, Susan M.
    Ripatti, Samuli
    Rivadeneira, Fernando
    Rudan, Igor
    Rustichini, Aldo
    Salomaa, Veikko
    Sarin, Antti-Pekka
    Schlessinger, David
    Scott, Rodney J.
    Snieder, Harold
    St Pourcain, Beate
    Starr, John M.
    Sul, Jae Hoon
    Surakka, Ida
    Svento, Rauli
    Teumer, Alexander
    Tiemeier, Henning
    van Rooij, Frank J. A.
    Van Wagoner, David R.
    Vartiainen, Erkki
    Viikari, Jorma
    Vollenweider, Peter
    Vonk, Judith M.
    Waeber, Gerard
    Weir, David R.
    Wichmann, H. -Erich
    Widen, Elisabeth
    Willemsen, Gonneke
    Wilson, James F.
    Wright, Alan F.
    Conley, Dalton
    Davey-Smith, George
    Franke, Lude
    Groenen, Patrick J. F.
    Hofman, Albert
    Johannesson, Magnus
    Kardia, Sharon L. R.
    Krueger, Robert F.
    Laibson, David
    Martin, Nicholas G.
    Meyer, Michelle N.
    Posthuma, Danielle
    Thurik, A. Roy
    Timpson, Nicholas J.
    Uitterlinden, Andre G.
    van Duijn, Cornelia M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Visscher, Peter M.
    Benjamin, Daniel J.
    Cesarini, David
    Koellinger, Philipp D.
    GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment2013Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 340, nr 6139, s. 1467-1471Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R-2 approximate to 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximate to 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

  • 194.
    Risérus, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Alcohol intake, insulin resistance, and abdominal obesity in elderly men2007Inngår i: Obesity (Silver Spring), ISSN 1930-7381, Vol. 15, nr 7, s. 1766-1773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Moderate and high alcohol intake have been associated with decreased and increased risk of type 2 diabetes, respectively. Insulin resistance, insulin secretion, and abdominal obesity are major predictors of diabetes, but the links with alcohol intake remain contradictory because of limited data. RESEARCH METHODS AND PROCEDURES: In a population-based cohort of 807 men (age, 70 years), we studied whether alcohol intake was related to insulin sensitivity, measured with the gold standard technique (euglycemic clamp), insulin secretion (early insulin response), or adiposity [BMI, waist circumference (WC), waist-to-hip ratio]. Alcohol intake was self-reported (questionnaire) and was assessed from a validated 7-day dietary record. The cross-sectional associations were evaluated using multivariable linear regression, adjusting for smoking, education level, physical activity, dietary total energy intake, hypertension, diabetes, triglycerides, and cholesterol. RESULTS: In multivariable models, self-estimated alcohol intake was not related to insulin sensitivity, early insulin response, or BMI, but was positively related to WC (beta-coefficient, 0.77; 95% confidence interval, 0.15 to 1.39; p=0.02) and waist-to-hip ratio (0.006 [0.002-0.009], p=0.003). The association with WC and waist-to-hip ratio was most pronounced in men in the lowest tertile of BMI. The results using dietary records were similar. DISCUSSION: Evaluated in a large sample in elderly men, neither insulin sensitivity measured by clamp technique nor insulin secretion was significantly associated with alcohol intake. However, high alcohol intake was associated with abdominal obesity, which might explain the higher diabetes risk previously observed in high alcohol consumers.

  • 195.
    Robinson, Matthew R.
    et al.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.;Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland..
    English, Geoffrey
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Moser, Gerhard
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Lloyd-Jones, Luke R.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Triplett, Marcus A.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Zhu, Zhihong
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Nolte, Ilja M.
    Univ Groningen, Dept Epidemiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    van Vliet-Ostaptchouk, Jana V.
    Univ Groningen, Dept Epidemiol, Univ Med Ctr Groningen, Groningen, Netherlands.;Univ Groningen, Dept Endocrinol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Snieder, Harold
    Univ Groningen, Dept Epidemiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Esko, Tonu
    Univ Tartu, Estonia Genome Ctr, Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol, Cambridge, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Milani, Lili
    Univ Tartu, Estonia Genome Ctr, Tartu, Estonia..
    Magi, Reedik
    Univ Tartu, Estonia Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonia Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    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, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Johannesson, Magnus
    Stockholm Sch Econ, Stockholm, Sweden..
    Yang, Jian
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Cesarini, David
    NYU, Dept Econ, Ctr Expt Social Sci, 550 1St Ave, New York, NY 10003 USA..
    Visscher, Peter M.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Genotype-covariate interaction effects and the heritability of adult body mass index2017Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 8, s. 1174-1181Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obesity is a worldwide epidemic, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 x 10(-18)), which contributed 8.1% (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 x 10(-5) and LRT = 30.80, P = 1.42 x 10(-8)), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01% of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI.

  • 196.
    Roos, Vendela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmo, Sweden..
    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.;.
    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.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Alterations in Multiple Lifestyle Factors in Subjects with the Metabolic Syndrome Independently of Obesity2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 118-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors. Methods: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI > 30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire. Results: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes. Conclusions: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

  • 197.
    Roos, Vendela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Div Geriatr Med, Dept Hlth Sci, Malmo, Sweden..
    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..
    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).
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Metabolic Syndrome Development During Aging with Special Reference to Obesity Without the Metabolic Syndrome2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 1, s. 36-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Obesity and its associated metabolic complications continue to increase worldwide. We investigated the development of metabolic syndrome (MetS) during aging in relation to body mass index (BMI) and exercise habits. We assigned special emphasis to the metabolic stability in individuals with obesity, but without MetS, a condition often referred to as metabolically healthy obesity. Materials and Methods: Cross-sectional analysis was carried out in a sample of 19,129 men and women aged 45-75 years from the EpiHealth study. In addition, longitudinal analyses were carried out in the ULSAM study (2322 men at baseline followed from age 50 to age 77) and in the PIVUS study (1016 men and women at baseline followed from age 70 to age 80). Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, National Cholesterol Education Program criteria). Results: MetS prevalence and number of MetS components increased with age in all three samples. The PIVUS study showed that high baseline BMI, low baseline physical activity, and increasing BMI during follow-up were related to increasing MetS prevalence and increasing numbers of MetS components during follow-up. One-third to half of individuals initially belonging to the obesity without MetS category acquired MetS during aging. Conclusions: MetS prevalence increased during aging, especially in individuals with high BMI, low level of physical activity, and weight gain. Obesity without MetS was not a stable condition over time as many of those individuals gained metabolic disturbances during aging.

  • 198.
    Roselli, Carolina
    et al.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Chaffin, Mark D.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Weng, Lu-Chen
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Aeschbacher, Stefanie
    Univ Hosp Basel, Basel, Switzerland;Cardiovasc Res Inst Basel, Basel, Switzerland.
    Ahlberg, Gustav
    Copenhagen Univ Hosp, Dept Cardiol, Heart Ctr, Lab Mol Cardiol,Rigshosp, Copenhagen, Denmark;Univ Copenhagen, Dept Biomed Sci, Danish Natl Res Fdn Ctr Cardiac Arrhythmia, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Albert, Christine M.
    Brigham & Womens Hosp, Div Prevent & Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
    Anderson, Christopher D.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Aragam, Krishna G.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Arking, Dan E.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
    Barnard, John
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit Dept, Seattle, WA 98195 USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Benjamin, Emelia J.
    NHLBI, Framingham, MA USA;Boston Univ, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA;Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA.
    Bihlmeyer, Nathan A.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet, Baltimore, MD USA.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Bloom, Heather L.
    Emory Univ, Div Cardiol, Atlanta, GA 30322 USA;Atlanta VA Med Ctr, Atlanta, GA USA.
    Boerwinkle, Eric
    Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Bottinger, Erwin B.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Calkins, Hugh
    Johns Hopkins Univ, Baltimore, MD USA.
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.
    Cappola, Thomas P.
    Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
    Carlquist, John
    Intermt Med Ctr, Intermt Heart Inst, Murray, UT USA;Univ Utah, Div Cardiovasc Med, Salt Lake City, UT USA.
    Chasman, Daniel I.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Harvard Med Sch, Boston, MA USA;Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.
    Chen, Lin Y.
    Univ Minnesota, Sch Med, Dept Med, Div Cardiovasc, Minneapolis, MN 55455 USA.
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Choi, Eue-Keun
    Seoul Natl Univ Hosp, Seoul, South Korea.
    Choi, Seung Hoan
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Christophersen, Ingrid E.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Drammen, Norway.
    Chung, Mina K.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Cole, John W.
    Baltimore Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA;Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
    Conen, David
    Univ Hosp Basel, Basel, Switzerland;Cardiovasc Res Inst Basel, Basel, Switzerland;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Cook, James
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Crijns, Harry J.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Cutler, Michael J.
    Intermt Med Ctr, Intermt Heart Inst, Murray, UT USA.
    Damrauer, Scott M.
    Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA;Corporal Michael Crescenz VA Med Ctr, Dept Surg, Philadelphia, PA USA.
    Daniels, Brian R.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Darbar, Dawood
    Univ Illinois, Chicago, IL USA.
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany.
    Denny, Joshua C.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Dichgans, Martin
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany;Munich Cluster Syst Neurol SyNergy, Munich, Germany;German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
    Dudink, Elton A.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Dudley, Samuel C.
    Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA;Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN USA.
    Esa, Nada
    Univ Massachusetts, Med Sch Worcester, Worcester, MA 01605 USA.
    Esko, Tonu
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Eskola, Markku
    Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
    Fatkin, Diane
    Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia;St Vincent Hosp, Darlinghurst, NSW, Australia;Univ New South Wales, Fac Med, Kensington, NSW, Australia.
    Felix, Stephan B.
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Franco, Oscar H.
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Geelhoed, Bastiaan
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Grewal, Raji P.
    St Francis Med Ctr, Dept Neurosci, Trenton, NJ USA;Seton Hall Univ, Sch Hlth & Med Sci, S Orange, NJ USA.
    Gudnason, Vilmundur
    Icelandic Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykavik, Iceland.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Gupta, Namrata
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gutmann, Rebecca
    Univ Iowa, Div Cardiovasc Med, Abboud Cardiovasc Res Ctr, Iowa City, IA USA.
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden.
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Heckbert, Susan R.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Hernesniemi, Jussi
    Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Hocking, Lynne J.
    Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
    Hofman, Albert
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Horimoto, Andrea R. V. R.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA.
    Huang, Paul L.
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Huffman, Jennifer
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. UStanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Ipek, Esra Gucuk
    Johns Hopkins Univ, Baltimore, MD USA.
    Ito, Kaoru
    RIKEN, Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.
    Jimenez-Conde, Jordi
    Inst Hosp Mar Invest Med, Hosp Mar, Dept Neurol, Neurovasc Res Grp IMIM, Barcelona, Spain;Univ Autonoma Barcelona, Med Dept, Barcelona, Spain.
    Johnson, Renee
    Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
    Kaeaeb, Stefan
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Center Tampere, Tampere, Finland.
    Kamatani, Yoichiro
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan.
    Kane, John P.
    Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
    Kastrati, Adnan
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany.
    Kathiresan, Sekar
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Katschnig-Winter, Petra
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Kavousi, Maryam
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Kessler, Thorsten
    Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany.
    Kietselaer, Bas L.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Kirchhof, Paulus
    Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England;Sandwell & West Birmingham Hosp NHS Trust, Birmingham, W Midlands, England;Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England;AFNET, Munster, Germany.
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany.
    Knight, Stacey
    Intermt Med Ctr, Intermt Heart Inst, Murray, UT USA;Univ Utah, Dept Med, Salt Lake City, UT 84112 USA.
    Krieger, Jose E.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Launer, Lenore J.
    NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
    Laurikka, Jari
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Center Tampere, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere Univ Hosp, Heart Ctr,Dept Cardiothoracic Surg, Tampere, Finland.
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Leineweber, Kirsten
    Bayer, Dept Dis Genom, Wuppertal, Germany.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Li, Man
    Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA;Univ Utah, Sch Med, Div Nephrol & Hypertens Internal Med, Salt Lake City, UT USA.
    Lim, Hong Euy
    Korea Univ, Guro Hosp, Seoul, South Korea.
    Lin, Henry J.
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Lin, Honghuang
    NHLBI, Framingham, MA USA;Boston Univ, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
    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.
    Lokki, Marja-Liisa
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland.
    London, Barry
    Univ Iowa, Div Cardiovasc Med, Abboud Cardiovasc Res Ctr, Iowa City, IA 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 USA.
    Low, Siew-Kee
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan.
    Lu, Yingchang
    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.
    Lyytikainen, Leo-Pekka
    Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Macfarlane, Peter W.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Malik, Rainer
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Mansur, Alfredo J.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Marcus, Gregory M.
    Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA.
    Margolin, Lauren
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Margulies, Kenneth B.
    Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
    Maerz, Winfried
    Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria;Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.
    McManus, David D.
    Univ Massachusetts, Med Sch Worcester, Worcester, MA 01605 USA.
    Melander, Olle
    Lund Univ, Dept Internal Med Clin Sci, Malmo, Sweden.
    Mohanty, Sanghamitra
    St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA;Dell Med Sch, Austin, TX USA.
    Montgomery, Jay A.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Morley, Michael P.
    Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Mueller-Nurasyid, Martina
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.
    Natale, Andrea
    St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA;Dell Med Sch, Austin, TX USA.
    Nazarian, Saman
    Univ Penn, Philadelphia, PA USA.
    Neumann, Benjamin
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany.
    Newton-Cheh, Christopher
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Niemeijer, Maartje N.
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Nikus, Kjell
    Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
    Nilsson, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Skane Univ Hosp, Malmo, Sweden.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    Oellers, Heidi
    Atrial Fibrillat NETwork, Munster, Germany.
    Olesen,