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  • 1. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Morley, Michael
    Wang, Xinchen
    Johnson, Andrew D
    Lundby, Alicia
    Gudbjartsson, Daníel F
    Noseworthy, Peter A
    Eijgelsheim, Mark
    Bradford, Yuki
    Tarasov, Kirill V
    Dörr, Marcus
    Müller-Nurasyid, Martina
    Lahtinen, Annukka M
    Nolte, Ilja M
    Smith, Albert Vernon
    Bis, Joshua C
    Isaacs, Aaron
    Newhouse, Stephen J
    Evans, Daniel S
    Post, Wendy S
    Waggott, Daryl
    Lyytikäinen, Leo-Pekka
    Hicks, Andrew A
    Eisele, Lewin
    Ellinghaus, David
    Hayward, Caroline
    Navarro, Pau
    Ulivi, Sheila
    Tanaka, Toshiko
    Tester, David J
    Chatel, Stéphanie
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kumari, Meena
    Morris, Richard W
    Naluai, Asa T
    Padmanabhan, Sandosh
    Kluttig, Alexander
    Strohmer, Bernhard
    Panayiotou, Andrie G
    Torres, Maria
    Knoflach, Michael
    Hubacek, Jaroslav A
    Slowikowski, Kamil
    Raychaudhuri, Soumya
    Kumar, Runjun D
    Harris, Tamara B
    Launer, Lenore J
    Shuldiner, Alan R
    Alonso, Alvaro
    Bader, Joel S
    Ehret, Georg
    Huang, Hailiang
    Kao, W H Linda
    Strait, James B
    Macfarlane, Peter W
    Brown, Morris
    Caulfield, Mark J
    Samani, Nilesh J
    Kronenberg, Florian
    Willeit, Johann
    Smith, J Gustav
    Greiser, Karin H
    Meyer Zu Schwabedissen, Henriette
    Werdan, Karl
    Carella, Massimo
    Zelante, Leopoldo
    Heckbert, Susan R
    Psaty, Bruce M
    Rotter, Jerome I
    Kolcic, Ivana
    Polašek, Ozren
    Wright, Alan F
    Griffin, Maura
    Daly, Mark J
    Arnar, David O
    Hólm, Hilma
    Thorsteinsdottir, Unnur
    Denny, Joshua C
    Roden, Dan M
    Zuvich, Rebecca L
    Emilsson, Valur
    Plump, Andrew S
    Larson, Martin G
    O'Donnell, Christopher J
    Yin, Xiaoyan
    Bobbo, Marco
    D'Adamo, Adamo P
    Iorio, Annamaria
    Sinagra, Gianfranco
    Carracedo, Angel
    Cummings, Steven R
    Nalls, Michael A
    Jula, Antti
    Kontula, Kimmo K
    Marjamaa, Annukka
    Oikarinen, Lasse
    Perola, Markus
    Porthan, Kimmo
    Erbel, Raimund
    Hoffmann, Per
    Jöckel, Karl-Heinz
    Kälsch, Hagen
    Nöthen, Markus M
    den Hoed, Marcel
    Loos, Ruth J F
    Thelle, Dag S
    Gieger, Christian
    Meitinger, Thomas
    Perz, Siegfried
    Peters, Annette
    Prucha, Hanna
    Sinner, Moritz F
    Waldenberger, Melanie
    de Boer, Rudolf A
    Franke, Lude
    van der Vleuten, Pieter A
    Beckmann, Britt Maria
    Martens, Eimo
    Bardai, Abdennasser
    Hofman, Nynke
    Wilde, Arthur A M
    Behr, Elijah R
    Dalageorgou, Chrysoula
    Giudicessi, John R
    Medeiros-Domingo, Argelia
    Barc, Julien
    Kyndt, Florence
    Probst, Vincent
    Ghidoni, Alice
    Insolia, Roberto
    Hamilton, Robert M
    Scherer, Stephen W
    Brandimarto, Jeffrey
    Margulies, Kenneth
    Moravec, Christine E
    Greco M, Fabiola Del
    Fuchsberger, Christian
    O'Connell, Jeffrey R
    Lee, Wai K
    Watt, Graham C M
    Campbell, Harry
    Wild, Sarah H
    El Mokhtari, Nour E
    Frey, Norbert
    Asselbergs, Folkert W
    Mateo Leach, Irene
    Navis, Gerjan
    van den Berg, Maarten P
    van Veldhuisen, Dirk J
    Kellis, Manolis
    Krijthe, Bouwe P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Franco, Oscar H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hofman, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kors, Jan A
    Uitterlinden, André G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Witteman, Jacqueline C M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kedenko, Lyudmyla
    Lamina, Claudia
    Oostra, Ben A
    Abecasis, Gonçalo R
    Lakatta, Edward G
    Mulas, Antonella
    Orrú, Marco
    Schlessinger, David
    Uda, Manuela
    Markus, Marcello R P
    Völker, Uwe
    Snieder, Harold
    Spector, Timothy D
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kähönen, Mika
    Mononen, Nina
    Raitakari, Olli T
    Viikari, Jorma S
    Adamkova, Vera
    Kiechl, Stefan
    Brion, Maria
    Nicolaides, Andrew N
    Paulweber, Bernhard
    Haerting, Johannes
    Dominiczak, Anna F
    Nyberg, Fredrik
    Whincup, Peter H
    Hingorani, Aroon D
    Schott, Jean-Jacques
    Bezzina, Connie R
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferrucci, Luigi
    Gasparini, Paolo
    Wilson, James F
    Rudan, Igor
    Franke, Andre
    Mühleisen, Thomas W
    Pramstaller, Peter P
    Lehtimäki, Terho J
    Paterson, Andrew D
    Parsa, Afshin
    Liu, Yongmei
    van Duijn, Cornelia M
    Siscovick, David S
    Gudnason, Vilmundur
    Jamshidi, Yalda
    Salomaa, Veikko
    Felix, Stephan B
    Sanna, Serena
    Ritchie, Marylyn D
    Stricker, Bruno H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stefansson, Kari
    Boyer, Laurie A
    Cappola, Thomas P
    Olsen, Jesper V
    Lage, Kasper
    Schwartz, Peter J
    Kääb, Stefan
    Chakravarti, Aravinda
    Ackerman, Michael J
    Pfeufer, Arne
    de Bakker, Paul I W
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 8, p. 826-836Article in journal (Refereed)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 2.
    Bandaru, Manoj Kumar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Emmanouilidou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Erik, Ingelsson
    Department of Medicine, Division of Cardiovascular Medicine, Stanford University.
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Apoc2 mutant zebrafish: a model for hypertriglyceridemia and early-stage atherosclerosisManuscript (preprint) (Other academic)
    Abstract [en]

    Zebrafish larvae in a hypertriglyceridemic background can be useful to identify and characterize causal genes for triglyceride metabolism. A previous, small-scale study suggested that apolipoprotein C-II (apoc2)-mutant zebrafish larvae can be used to model hypertriglyceridemia-induced atherosclerosis. We aimed to replicate these findings in a large-scale study and asses if APOC-II may represent a useful therapeutic target. We generated apoc2 mutant zebrafish using CRISPR-Cas9 and examined cardiometabolomic traits in their offspring (F1 generation). Systematic characterization of 384 larvae using our image and assay-based, high-throughput pipeline showed that compound heterozygous larvae for loss of function mutations in apoc2 (n=35) have higher whole-body levels of triglycerides (0.71±0.16 SD), HDL cholesterol (0.32±0.15 SD) and total cholesterol (0.37±0.18 SD), and a trend for lower whole-body glucose levels (0.23±0.14 SD) compared with larvae without mutations in apoc2 (n=174). Such larvae also tended to have more vascular lipid deposition, however this effect did not reach significance (P=0.12). Interestingly, the trends for lower whole-body glucose levels and more vascular lipid deposition in larvae with anticipated loss of functional apoc2 reached significance when larvae (n=3812) from other screens, in which apoc2 was not experimentally perturbed were included as additional wildtype controls. Thus, our large-scale study confirms the role of apoc2 in hypertriglyceridemia and early-stage atherosclerosis. While apoc2 mutant zebrafish model can be used as a genetic background to identify and characterize causal genes for triglyceride metabolism, independent and opposite effects on triglycerides and glucose suggest that APOC-II is likely not a suitable target for prevention and treatment of coronary artery disease.

  • 3.
    Bandaru, Manoj Kumar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Mazzaferro, Eugenia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Emmanouilidou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Erik, Ingelsson
    Department of Medicine, Division of Cardiovascular Medicine, Stanford University.
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Image-based, in vivo characterization of cardiometabolic consequences of mutations in pcsk9Manuscript (preprint) (Other academic)
    Abstract [en]

    Based on the association of loss-of-function mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) with low plasma LDL cholesterol levels, inhibition of the PCSK9 protein using monoclonal antibodies have emerged as an effective treatment option to lower LDL cholesterol levels and reduce the risk of coronary artery disease. Despite these beneficial effects, PCSK9 inhibitors may increase the risk of diabetes. In this study, we mimicked the mechanistic action of PCSK9 inhibitors in humans by inducing mutations in pcsk9 in zebrafish and examining their effects on dyslipidemia, early-stage atherosclerosis and diabetes-related traits in data from nearly 5000 zebrafish larvae. At 10 days of age, larvae with mutations in pcsk9 were characterized by lower whole-body LDL cholesterol levels (beta±SE -0.056±0.025 SD units) and protection against early-stage atherosclerosis, with less vascular lipid deposition (-0.133±0.035 SD) and less co-localization of macrophages with lipids (-0.086±0.032 SD). Mutant larvae also had fewer pancreatic β-cells (-0.153±0.055 SD). Thus, our findings in pcsk9 mutant larvae are in line with results from people carrying loss-of-function PCSK9 mutations, and are also in line with the effects of PCSK9 inhibitors in humans. Further, our results suggest that mutations in pcsk9 may increase the risk of diabetes through a direct effect on pancreatic β-cells.

  • 4.
    Barban, Nicola
    et al.
    Univ Oxford, Dept Sociol, Oxford, England.;Univ Oxford, Nuffield Coll, Oxford, England..
    Jansen, Rick
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands..
    de Vlaming, Ronald
    Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Esfahan, Iran..
    Mandemakers, Jornt J.
    Wageningen Univ Res, Sociol Consumpt & Households, Wageningen, Netherlands..
    Tropf, Felix C.
    Univ Oxford, Dept Sociol, Oxford, England.;Univ Oxford, Nuffield Coll, Oxford, England..
    Shen, Xia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Wilson, James F.
    Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Chasman, Daniel I.
    Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Nolte, Illa M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands..
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Perry, John R. B.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Kong, Augustine
    Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland.;Amgen Inc, deCODE Genet, Reykjavik, Iceland..
    Ahluwalia, Tarunveer S.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Steno Diabet Ctr, Gentofte, Denmark.;Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark..
    Albrecht, Eva
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany..
    Yerges-Armstrong, Laura
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA..
    Atzmon, Gil
    Albert Einstein Coll Med, Dept Med, Inst Aging Res, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Inst Aging Res, Dept Genet, Bronx, NY 10467 USA.;Univ Haifa, Dept Nat Sci, Haifa, Israel..
    Auro, Kirsi
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland..
    Ayers, Kristin
    Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Bakshi, Andrew
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Ben-Avraham, Danny
    Albert Einstein Coll Med, Inst Aging Res, Dept Genet, Bronx, NY 10467 USA..
    Berger, Klaus
    Univ Munster, Inst Epidemiol & Social Med, Munster, Germany..
    Bergman, Aviv
    Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA..
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Inst Neurogenet, Lubeck, Germany.;Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;Imperial Coll, Fac Med, Sch Publ Hlth, London, England..
    Bielak, Lawrence F.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Bjornsdottir, Gyda
    Amgen Inc, deCODE Genet, Reykjavik, Iceland..
    Bonder, Marc Jan
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Genom Coordinat Ctr, Groningen, Netherlands..
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Bui, Minh
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia..
    Barbieri, Caterina
    San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy..
    Cavadino, Alana
    UCL Inst Child Hlth, Populat Policy & Practice, London, England.;Queen Mary Univ London, Wolfson Inst Preventat Med, Ctr Environm & Prevent Med, London, England..
    Chavarro, Jorge E.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Turman, Constance
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Concas, Maria Pina
    CNR, UOS Sassari, Inst Genet & Biomed Res, Sassari, Italy..
    Cordell, Heather J.
    Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Eibich, Peter
    Univ Oxford, Hlth Econ Res Ctr, Oxford, England..
    Eriksson, Nicholas
    23andMe Inc, Mountain View, CA USA..
    Esko, Tonu
    Broad Inst MIT & Harvard, Cambridge, MA USA..
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Falahi, Fahimeh
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Felix, Janine F.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands..
    Fontana, Mark Alan
    Univ Southern Calif, Ctr Econ & Social Res, Los Angeles, CA USA..
    Franke, Lude
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Genom Coordinat Ctr, Groningen, Netherlands..
    Gandin, Ilaria
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Gaskins, Audrey J.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Gunderson, Erica P.
    Kaiser Permanente Northern Calif, Div Res, Cardiovasc & Metab Condit Sect, Oakland, CA USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    He, Chunyan
    Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA..
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
    Huang, Hongyan
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Kifley, Annette
    Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Westmead, NSW, Australia.;Univ Sydney, Westmead Inst Med Res, Westmead, NSW, Australia..
    Kluttig, Alexander
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol Biostat & Informat, Halle, Saale, Germany..
    Kraft, Peter
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Lagou, Vasiliki
    Katholieke Univ Leuven, Dept Neurosci, Leuven, Belgium.;Katholieke Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium.;VIB, Translat Immunol Lab, Leuven, Belgium..
    Lecoeur, Cecile
    Univ Lille, CNRS, Inst Pasteur Lille, Lille, France..
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, Helsinki, Finland.;Univ Helsinki, Helsinki Coll Adv Studies, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Lind, Penelope A.
    QIMR Berghofer Med Res Inst, Psychiat Genet, Herston Brisbane, Qld, Australia..
    Liu, Tian
    Max Planck Inst Human Dev, Ctr Lifespan Psychol, Berlin, Germany.;Max Planck Inst Mol Genet, Dept Vertebrate Genom, Berlin, Germany..
    Makalic, Enes
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia..
    Mamasoula, Crysovalanto
    Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Matteson, Lindsay
    Univ Minnesota, Dept Psychol, Minnesota Ctr Twin & Family Res, Minneapolis, MN USA..
    Mbarek, Hamdi
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    McArdle, Patrick F.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA..
    McMahon, George
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England..
    Meddens, S. Fleur W.
    Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.;Vrije Univ Amsterdam, Complex Trait Genet, Amsterdam, Netherlands..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Miller, Mike
    Univ Minnesota, Dept Psychol, Minneapolis, MN USA..
    Missmer, Stacey A.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Monnereau, Claire
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Myhre, Ronny
    Inst Publ Hlth, Area Hlth Data & Digitalizat, Dept Genet & Bioinformat, Oslo, Norway..
    Nalls, Mike A.
    NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Nutile, Teresa
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy..
    Kalafati, Ioanna Panagiota
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Porcu, Eleonora
    Cittadella Univ Monserrato, Ist Ric Genet & Biomed, CMR, Cagliari, Italy.;Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy..
    Prokopenko, Inga
    Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rajan, Kumar B.
    Rush Univ, Med Ctr, Chicago, IL 60612 USA..
    Rich-Edwards, Janet
    Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Rietveld, Cornelius A.
    Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands..
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Rose, Lynda M.
    Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Rueedi, Rico
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Ryan, Kathleen-A
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA..
    Saba, Yasaman
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
    Schmidt, Daniel
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia..
    Smith, Jennifer A.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Streeten, Elizabeth
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA..
    Toenjes, Anke
    Univ Leipzig, Dept Med, Leipzig, Germany..
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland..
    Ulivi, Sheila
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Wedenoja, Juho
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Wellmann, Juergen
    Univ Munster, Inst Epidemiol & Social Med, Munster, Germany..
    Willeit, Peter
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.;Kings British Heart Fdn Ctr, Kings Coll London, London, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Yao, Jie
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Yengo, Loic
    Univ Lille, CNRS, Inst Pasteur Lille, Lille, France.;Univ Queensland, Ctr Neurogenet & Stat Genom, Brisbane, Qld, Australia..
    Zhao, Jing Hua
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Zhao, Wei
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Zhernakova, Dania V.
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Genom Coordinat Ctr, Groningen, Netherlands..
    Amin, Najaf
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Andrews, Howard
    New York State Psychiat Inst & Hosp, Data Coordinating Ctr, New York, NY 10032 USA..
    Balkau, Beverley
    Univ Lille, CNRS, Inst Pasteur Lille, Lille, France..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, Inst Aging Res, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA..
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Biino, Ginevra
    Natl Res Council Italy, Inst Mol Genet, Pavia, Italy..
    Bisgaard, Hans
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark..
    Bonnelykke, Klaus
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Buring, Julie E.
    Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Cappellani, Stefania
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Ciullo, Marina
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Cox, Simon R.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Cucca, Francesco
    Cittadella Univ Monserrato, Ist Ric Genet & Biomed, CMR, Cagliari, Italy.;Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy..
    Toniolo, Daniela
    San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy..
    Davey-Smith, George
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    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, Saudi Arabia..
    van Duijn, Cornelia M.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    de Geus, Eco J. C.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland.;Vasa Cent Hosp, Vaasa, Finland..
    Evans, Denis A.
    Rush Univ, Med Ctr, Chicago, IL 60612 USA..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Sala, Cinzia Felicita
    San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy..
    Froguel, Philippe
    Univ Lille, CNRS, Inst Pasteur Lille, Lille, France..
    Gasparini, Paolo
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.;Sidra, Div Expt Genet, Doha, Qatar..
    Girotto, Giorgia
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.;Sidra, Div Expt Genet, Doha, Qatar..
    Grabe, Hans-Joergen
    Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Greiser, Karin Halina
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany..
    Groenen, Patrick J. F.
    Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.;Erasmus Univ, Erasmus Sch Econ, Econometric Inst, Rotterdam, Netherlands..
    de Haan, Hugoline G.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Haerting, Johannes
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol Biostat & Informat, Halle, Saale, Germany..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Heath, Andrew C.
    QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia..
    Heikkila, Kauko
    Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland..
    Hofman, Albert
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany..
    Holliday, Elizabeth G.
    Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia.;Hunter Med Res Inst, Newcastle, NSW, Australia..
    Hopper, John
    Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia..
    Hypponen, Elina
    UCL Inst Child Hlth, Populat Policy & Practice, London, England.;Univ South Australia, Sansom Inst Hlth Res, Ctr Populat Hlth Res, Adelaide, SA, Australia.;Univ South Australia, Sch Hlth Sci, Adelaide, SA, Australia.;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    Jacobsson, Bo
    Inst Publ Hlth, Area Hlth Data & Digitalizat, Dept Genet & Bioinformat, Oslo, Norway.;Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Jaddoe', Vincent W. V.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands..
    Johannesson, Magnus
    Stockholm Sch Econ, Dept Econ, Stockholm, Sweden..
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland.;Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland..
    Kajantie, Eero
    Helsinki Univ Cent Hosp, Childrens Hosp, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.;Oulu Univ Hosp, MRC Oulu, Dept Obstet & Gynecol, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    Kardia, Sharon L. R.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Keavney, Bernard
    Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England.;Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England..
    Kolcic, Ivana
    Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia..
    Koponen, Paivikki
    Natl Inst Hlth & Welf, Hlth Monitoring Unit, Helsinki, Finland..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany..
    Kronenberg, Florian
    Med Univ Innsbruck, Div Genet Epidemiol, Innsbruck, Austria..
    Kutalik, Zoltan
    Swiss Inst Bioinformat, Lausanne, Switzerland.;Lausanne Univ Hosp CHUV, Inst Social & Prevent Med, Lausanne, Switzerland..
    La Bianca, Martina
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Lachance, Genevieve
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Iacono, William G.
    Univ Minnesota, Dept Psychol, Minneapolis, MN USA..
    Lai, Sandra
    Cittadella Univ Monserrato, Ist Ric Genet & Biomed, CMR, Cagliari, Italy..
    Lehtimaki, Terho
    Univ Tampere, Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Liewald, David C.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland..
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;NIHR Oxford Biomed Res Ctr, Oxford, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Luben, Robert
    Univ Cambridge, Strangeways Res Lab, Cambridge, England..
    Lucht, Michael
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Luoto, Riitta
    UKK Inst Hlth Promot, Tampere, Finland..
    Magnus, Per
    Inst Publ Hlth, Area Hlth Data & Digitalizat, Dept Genet & Bioinformat, Oslo, Norway..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Psychiat Genet, Herston Brisbane, Qld, Australia..
    McGue, Matt
    Univ Minnesota, Dept Psychol, Minneapolis, MN USA.;Univ Southern Denmark, Inst Publ Hlth, Danish Aging Res Ctr, Odense, Denmark.;Univ Southern Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark..
    McQuillan, Ruth
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Psychiat Genet, Herston Brisbane, Qld, Australia..
    Meisinger, Christa
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Cent Hosp Augsburg, MONICA KORA Myocardial Infarct Registry, Augsburg, Germany..
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia..
    Traglia, Michela
    San Raffaele Res Inst, Div Genet & Cell Biol, Milan, Italy..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mitchell, Paul
    Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Westmead, NSW, Australia.;Univ Sydney, Westmead Inst Med Res, Westmead, NSW, Australia..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia.;Univ Queensland, Mol Biosci, Brisbane, Qld, Australia..
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.;King Faisal Specialist Hosp & Res Ctr, Epidemiol Sect, Dept BESC, Riyadh, Saudi Arabia..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Nohr, Ellen A.
    Univ Southern Denmark, Dept Clin Res, Res Unit Gynecol & Obstet, Odense, Denmark..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Olsen, Porn
    Aarhus Univ, Dept Clin Epidemiol, Aarhus, Denmark..
    Ong, Ken K.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Paternoster, Lavinia
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Perola, Markus
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Peyser, Patricia A.
    Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Pirastu, Mario
    CNR, UOS Sassari, Inst Genet & Biomed Res, Sassari, Italy..
    Polasek, Ozren
    Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia..
    Power, Chris
    UCL Inst Child Hlth, Populat Policy & Practice, London, England..
    Kaprio, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Raffel, Leslie J.
    Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA..
    Raikkonen, Katri
    Univ Helsinki, Inst Behav Sci, Helsinki, Finland..
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland..
    Ridker, Paul M.
    Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Ring, Susan M.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Roll, Kathryn
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy..
    Rujescu, Dan
    Martin Luther Univ Halle Wittenberg, Dept Psychiat, Halle, Saale, Germany..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Schlessinger, David
    NIA, Lab Genet, Baltimore, MD 21224 USA..
    Schmidt, Helena
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
    Schupf, Nicole
    Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA.;Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA..
    Smit, Johannes
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Sorice, Rossella
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Stockl, Doris
    Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA.;Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA..
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Stumvoll, Michael
    Univ Leipzig, Dept Med, Leipzig, Germany.;Univ Leipzig, IFB Adipos Dis, Leipzig, Germany..
    Swertz, Morris A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Genom Coordinat Ctr, Groningen, Netherlands..
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Thurik, A. Roy
    Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.;Montpellier Business Sch, Montpellier, France..
    Timpson, Nicholas J.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Tung, Joyce Y.
    23andMe Inc, Mountain View, CA USA..
    Uitterlinden, Andre G.
    Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Vaccargiu, Simona
    CNR, UOS Sassari, Inst Genet & Biomed Res, Sassari, Italy..
    Viikari, Jorma
    Univ Turku, Dept Med, Turku, Finland.;Turku Univ Hosp, Div Med, Turku, Finland..
    Vitart, Veronique
    Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Vollenweider, Peter
    Lausanne Univ Hosp CHUV, Dept Internal Med, Lausanne, Switzerland..
    Vuckovic, Dragana
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.;Sidra, Div Expt Genet, Doha, Qatar..
    Waage, Johannes
    Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark..
    Wagner, Gert G.
    Max Planck Inst Human Dev, German Socioecon Panel Study SOEP, Berlin, Germany.;Berlin Univ Technol TUB, Berlin, Germany..
    Wang, Jie Jin
    Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Westmead, NSW, Australia.;Univ Sydney, Westmead Inst Med Res, Westmead, NSW, Australia..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Weir, David R.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Willemsen, Gonneke
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.;EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Wright, Alan F.
    Univ Edinburgh, MRC Human Genet Unit, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Zondervan, Krina T.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England.;Univ Oxford, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford, England..
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Krueger, Robert F.
    Univ Minnesota, Dept Psychol, Minneapolis, MN USA..
    Lee, James J.
    Univ Minnesota, Dept Psychol, Minneapolis, MN USA..
    Benjamin, Daniel J.
    Univ Southern Calif, Ctr Econ & Social Res, Los Angeles, CA USA.;Natl Bur Econ Res, Cambridge, MA 02138 USA..
    Cesarini, David
    NYU, Dept Econ, New York, NY 10003 USA.;Res Inst Ind Econ, Stockholm, Sweden..
    Koellinger, Philipp D.
    Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands.;Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.;Vrije Univ Amsterdam, Complex Trait Genet, Amsterdam, Netherlands..
    den Hoed, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Mills, Melinda C.
    Univ Oxford, Dept Sociol, Oxford, England.;Univ Oxford, Nuffield Coll, Oxford, England..
    Genome-wide analysis identifies 12 loci influencing human reproductive behavior2016In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 12, p. 1462-1472Article in journal (Refereed)
    Abstract [en]

    The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

  • 5.
    Deleskog, Anna
    et al.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, POB 210, S-17177 Stockholm, Sweden..
    den Hoed, Marcel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Tettamanti, Giorgio
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, POB 210, S-17177 Stockholm, Sweden..
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, POB 210, S-17177 Stockholm, Sweden..
    Ljung, Rickard
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, POB 210, S-17177 Stockholm, Sweden..
    Feychting, Maria
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, POB 210, S-17177 Stockholm, Sweden..
    Brooke, Hannah L.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, POB 210, S-17177 Stockholm, Sweden..
    Maternal diabetes and incidence of childhood cancer: a nationwide cohort study and exploratory genetic analysis2017In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, p. 633-642Article in journal (Refereed)
    Abstract [en]

    Background: The etiology of childhood cancer is not well understood, but may be linked to prenatal and perinatal factors, such as maternal diabetes. However, this association has not been examined in depth. We aimed to determine if maternal diabetes is associated with risk of childhood brain tumor (CBT), leukemia (all types combined and acute lymphoblastic leukemia [ALL] separately), and lymphoma.

    Methods: All children born in Sweden between 1973 and 2014 (n= 4,239,965) were followed from birth until first cancer diagnosis, age 15 years, or December 31, 2015. Data on maternal diabetes, childhood cancer, and covariates were obtained from nationwide health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using Cox regression adjusted for potential confounders/mediators. Additionally, we performed an exploratory analysis using results from published genome-wide association studies and functional annotation.

    Results: Maternal diabetes was associated with lower risk of CBT (adjusted IRR [95% CI]: 0.56 [0.35-0.91]) and higher risk of leukemia (adjusted IRR: 1.47 [1.13-1.92] for all leukemia combined and 1.64 [1.23-2.18] for ALL). These associations were similar for both maternal type 1 diabetes and gestational diabetes. Associations of five previously identified genetic loci were compatible with a causal effect of diabetes traits on neuroblastoma and common Hodgkin's lymphoma.

    Conclusion: Children whose mother had diabetes had lower risk of CBT and higher risk of leukemia, compared with children whose mother did not have diabetes. Our results are compatible with a role of prenatal and perinatal glycemic environment in childhood cancer etiology.

  • 6. den Hoed, M
    et al.
    Hesselink, M K C
    Westerterp, K R
    Skeletal muscle fiber-type distribution and habitual physical activity in daily life.2009In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 19, no 3Article in journal (Refereed)
    Abstract [en]

    The capacity to perform physical activity largely depends on physical fitness. Muscle fiber-type distribution (Muscle(FTD)) is associated with physical fitness and may influence the capacity to perform physical activity. The purpose of this study was to determine whether habitual physical activity in daily life (PA(DL)) and Muscle(FTD) are related. Thirty-eight healthy non-athletes (31 women, 7 men) were recruited. PA(DL) was measured twice for 14 days using a tri-axial accelerometer for movement registration (Tracmor). From Tracmor output, the proportion of time subjects were physically active at low, moderate, and high intensities was determined (%Low, %Moderate, and %High, respectively). A total activity index (PA(index)) and sub-scores on work, leisure-time and sports were obtained using the Baecke questionnaire. Muscle(FTD) was determined using immuno-fluorescence against respective myosin heavy chain isoforms. No relationship was observed between PA(DL) and Muscle(FTD). %Low, %Moderate, and %High, as well as PA(index) and its sub-scores, were not related to Muscle(FTD) either. The time spent on sports was associated with the proportion of type I and II(X) fibers (P=0.06 and P<0.01, respectively). In conclusion, Muscle(FTD) probably cannot explain why some people are more prone to engaging in physical activities than others.

  • 7. den Hoed, M
    et al.
    Luan, J
    Langenberg, C
    Cooper, C
    Sayer, A A
    Jameson, K
    Kumari, M
    Kivimaki, M
    Hingorani, A D
    Grøntved, A
    Khaw, K-T
    Ekelund, U
    Wareham, N J
    Loos, R J F
    Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples.2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.

    OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based samples.

    DESIGN: Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.

    RESULTS: We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (β=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).

    CONCLUSION: Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.

  • 8. den Hoed, M
    et al.
    Smeets, A J P G
    Veldhorst, M A B
    Nieuwenhuizen, A G
    Bouwman, F G
    Heidema, A G
    Mariman, E C M
    Westerterp-Plantenga, M S
    Westerterp, K R
    SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis.2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The postprandial responses in (an)orexigenic hormones and feelings of hunger are characterized by large inter-individual differences. Food intake regulation was shown earlier to be partly under genetic control.

    OBJECTIVE: This study aimed to determine whether the postprandial responses in (an)orexigenic hormones and parameters of food intake regulation are associated with single nucleotide polymorphisms (SNPs) in genes encoding for satiety hormones and their receptors.

    DESIGN: Peptide YY (PYY), glucagon-like peptide 1 and ghrelin levels, as well as feelings of hunger and satiety, were determined pre- and postprandially in 62 women and 41 men (age 31+/-14 years; body mass index 25.0+/-3.1 kg/m(2)). Dietary restraint, disinhibition and perceived hunger were determined using the three-factor eating questionnaire. SNPs were determined in the GHRL, GHSR, LEP, LEPR, PYY, NPY, NPY2R and CART genes.

    RESULTS: The postprandial response in plasma ghrelin levels was associated with SNPs in PYY (215G>C, P<0.01) and LEPR (326A>G and 688A>G, P<0.01), and in plasma PYY levels with SNPs in GHRL (-501A>C, P<0.05) and GHSR (477G>A, P<0.05). The postprandial response in feelings of hunger was characterized by an SNP-SNP interaction involving SNPs in LEPR and NPY2R (668A>G and 585T>C, P<0.05). Dietary restraint and disinhibition were associated with an SNP in GHSR (477G>A, P<0.05), and perceived hunger with SNPs in GHSR and NPY (477G>A and 204T>C, P<0.05).

    CONCLUSIONS: Part of the inter-individual variability in postprandial responses in (an)orexigenic hormones can be explained by genetic variation. These postprandial responses represent either long-term physiological adaptations to facilitate homeostasis or reinforce direct genetic effects.

  • 9. den Hoed, M
    et al.
    Westerterp, K R
    Body composition is associated with physical activity in daily life as measured using a triaxial accelerometer in both men and women.2008In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 32, no 8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Activity-related energy expenditure is the most variable component of total energy expenditure and thus an important determinant of energy balance.

    OBJECTIVE: To determine whether body composition is related to physical activity in both men and women.

    DESIGN: A total of 134 healthy participants were recruited (80 women, 54 men; aged 21+/-2 years; body mass index, 22.0+/-2.4). Physical activity was measured for a period of 2 weeks using a triaxial accelerometer for movement registration (Tracmor). Percentage body fat (%BF) was determined by underwater weighing and deuterium dilution according to Siri's three-compartment model.

    RESULTS: The participant characteristics-body mass, height and gender together explained a substantial part of the variation in %BF (R(2)=0.75, SEE=4.0%). Adding physical activity to the model increased the explained variation in %BF with 4% (R(2)=0.79, SEE=3.7%, P<0.001). Taking seasonality into account by adding the number of daylight hours as an independent variable further increased the explained variation with 1% (R(2)=0.80, SEE=3.7%, P<0.05). In analogy, the association was evaluated for both genders separately. In women, %BF and physical activity were significantly associated (P<0.001). In men, %BF was only associated with physical activity when seasonality was taken into account as well (P<0.05). This probably resulted from men participating more in season bound sports, because an association was found without adjusting for seasonality when only men with a consistent year-round participation in sports were considered.

    CONCLUSION: Evidence was found for an association between body composition and physical activity in both genders. A consistent year-round degree of physical activity appears to be a prerequisite to reveal the association. Moreover, Tracmor-assessed physical activity improves the estimate of %BF when a participant's characteristics are taken into account.

  • 10.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Brage, Soren
    Zhao, Jing Hua
    Westgate, Kate
    Nessa, Ayrun
    Ekelund, Ulf
    Spector, Tim D.
    Wareham, Nicholas J.
    Loos, Ruth J. F.
    Heritability of objectively assessed daily physical activity and sedentary behavior2013In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 98, no 5, p. 1317-1325Article in journal (Refereed)
    Abstract [en]

    Background: Twin and family studies that estimated the heritability of daily physical activity have been limited by poor measurement quality and a small sample size. Objective: We examined the heritability of daily physical activity and sedentary behavior assessed objectively by using combined heart rate and movement sensing in a large twin study. Design: Physical activity traits were assessed in daily life for a mean (+/- SD) 6.7 +/- 1.1 d in 1654 twins from 420 monozygotic and 352 dizygotic same-sex twin pairs aged 56.3 +/- 10.4 y with body mass index (in kg/m(2)) of 26.1 +/- 4.8. We estimated the average daily movement, physical activity energy expenditure, and time spent in moderate-to-vigorous intensity physical activity and sedentary behavior from heart rate and acceleration data. We used structural equation modeling to examine the contribution of additive genetic, shared environmental, and unique environmental factors to between-individual variation in traits. Results: Additive genetic factors (le, heritability) explained 47% of the variance in physical activity energy expenditure (95% CI: 23%, 53%) and time spent in moderate-to-vigorous intensity physical activity (95% CI: 29%, 54%), 35% of the variance in acceleration of the trunk (95% CI: 0%, 44%), and 31% of the variance in the time spent in sedentary behavior (95% CI: 9%, 51%). The remaining variance was predominantly explained by unique environmental factors and random error, whereas shared environmental factors played only a marginal role for all traits with a range of 0-15%. Conclusions: The between-individual variation in daily physical activity and sedentary behavior is mainly a result of environmental influences. Nevertheless, genetic factors explain up to one-half of the variance, suggesting that innate biological processes may be driving some of our daily physical activity.

  • 11.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eijgelsheim, Mark
    Esko, Tonu
    Brundel, Bianca J. J. M.
    Peal, David S.
    Evans, David M.
    Nolte, Ilja M.
    Segre, Ayellet V.
    Holm, Hilma
    Handsaker, Robert E.
    Westra, Harm-Jan
    Johnson, Toby
    Isaacs, Aaron
    Yang, Jian
    Lundby, Alicia
    Zhao, Jing Hua
    Kim, Young Jin
    Go, Min Jin
    Almgren, Peter
    Bochud, Murielle
    Boucher, Gabrielle
    Cornelis, Marilyn C.
    Gudbjartsson, Daniel
    Hadley, David
    van der Harst, Pim
    Hayward, Caroline
    den Heijer, Martin
    Igl, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Jackson, Anne U.
    Kutalik, Zoltan
    Luan, Jian'an
    Kemp, John P.
    Kristiansson, Kati
    Ladenvall, Claes
    Lorentzon, Mattias
    Montasser, May E.
    Njajou, Omer T.
    O'Reilly, Paul F.
    Padmanabhan, Sandosh
    Pourcain, Beate St.
    Rankinen, Tuomo
    Salo, Perttu
    Tanaka, Toshiko
    Timpson, Nicholas J.
    Vitart, Veronique
    Waite, Lindsay
    Wheeler, William
    Zhang, Weihua
    Draisma, Harmen H. M.
    Feitosa, Mary F.
    Kerr, Kathleen F.
    Lind, Penelope A.
    Mihailov, Evelin
    Onland-Moret, N. Charlotte
    Song, Ci
    Weedon, Michael N.
    Xie, Weijia
    Yengo, Loic
    Absher, Devin
    Albert, Christine M.
    Alonso, Alvaro
    Arking, Dan E.
    de Bakker, Paul I. W.
    Balkau, Beverley
    Barlassina, Cristina
    Benaglio, Paola
    Bis, Joshua C.
    Bouatia-Naji, Nabila
    Brage, Soren
    Chanock, Stephen J.
    Chines, Peter S.
    Chung, Mina
    Darbar, Dawood
    Dina, Christian
    Doerr, Marcus
    Elliott, Paul
    Felix, Stephan B.
    Fischer, Krista
    Fuchsberger, Christian
    de Geus, Eco J. C.
    Goyette, Philippe
    Gudnason, Vilmundur
    Harris, Tamara B.
    Hartikainen, Anna-Liisa
    Havulinna, Aki S.
    Heckbert, Susan R.
    Hicks, Andrew A.
    Hofman, Albert
    Holewijn, Suzanne
    Hoogstra-Berends, Femke
    Hottenga, Jouke-Jan
    Jensen, Majken K.
    Johansson, Asa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Junttila, Juhani
    Kaeaeb, Stefan
    Kanon, Bart
    Ketkar, Shamika
    Khaw, Kay-Tee
    Knowles, Joshua W.
    Kooner, Angrad S.
    Kors, Jan A.
    Kumari, Meena
    Milani, Lili
    Laiho, Paeivi
    Lakatta, Edward G.
    Langenberg, Claudia
    Leusink, Maarten
    Liu, Yongmei
    Luben, Robert N.
    Lunetta, Kathryn L.
    Lynch, Stacey N.
    Markus, Marcello R. P.
    Marques-Vidal, Pedro
    Leach, Irene Mateo
    McArdle, Wendy L.
    McCarroll, Steven A.
    Medland, Sarah E.
    Miller, Kathryn A.
    Montgomery, Grant W.
    Morrison, Alanna C.
    Mueller-Nurasyid, Martina
    Navarro, Pau
    Nelis, Mari
    O'Connell, Jeffrey R.
    O'Donnell, Christopher J.
    Ong, Ken K.
    Newman, Anne B.
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Rao, Dabeeru C.
    Ring, Susan M.
    Rossin, Elizabeth J.
    Rudan, Diana
    Sanna, Serena
    Scott, Robert A.
    Sehmi, Jaban S.
    Sharp, Stephen
    Shin, Jordan T.
    Singleton, Andrew B.
    Smith, Albert V.
    Soranzo, Nicole
    Spector, Tim D.
    Stewart, Chip
    Stringham, Heather M.
    Tarasov, Kirill V.
    Uitterlinden, Andre G.
    Vandenput, Liesbeth
    Hwang, Shih-Jen
    Whitfield, John B.
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilson, James F.
    Witteman, Jacqueline C. M.
    Wong, Andrew
    Wong, Quenna
    Jamshidi, Yalda
    Zitting, Paavo
    Boer, Jolanda M. A.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    van Duijn, Cornelia M.
    Ekelund, Ulf
    Forouhi, Nita G.
    Froguel, Philippe
    Hingorani, Aroon
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kronmal, Richard A.
    Kuh, Diana
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Martin, Nicholas G.
    Oostra, Ben A.
    Pedersen, Nancy L.
    Quertermous, Thomas
    Rotter, Jerome I.
    van der Schouw, Yvonne T.
    Verschuren, W. M. Monique
    Walker, Mark
    Albanes, Demetrius
    Arnar, David O.
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Boehnke, Michael
    de Boer, Rudolf A.
    Bouchard, Claude
    Caulfield, W. L. Mark
    Chambers, John C.
    Curhan, Gary
    Cusi, Daniele
    Eriksson, Johan
    Ferrucci, Luigi
    van Gilst, Wiek H.
    Glorioso, Nicola
    de Graaf, Jacqueline
    Groop, Leif
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hsueh, Wen-Chi
    Hu, Frank B.
    Huikuri, Heikki V.
    Hunter, David J.
    Iribarren, Carlos
    Isomaa, Bo
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kiemeney, Lambertus A.
    van der Klauw, Melanie M.
    Kooner, Jaspal S.
    Kraft, Peter
    Iacoviello, Licia
    Lehtimaki, Terho
    Lokki, Marja-Liisa L.
    Mitchell, Braxton D.
    Navis, Gerjan
    Nieminen, Markku S.
    Ohlsson, Claes
    Poulter, Neil R.
    Qi, Lu
    Raitakari, Olli T.
    Rimm, Eric B.
    Rioux, John D.
    Rizzi, Federica
    Rudan, Igor
    Salomaa, Veikko
    Sever, Peter S.
    Shields, Denis C.
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stanton, Alice V.
    Stolk, Ronald P.
    Strachan, David P.
    Tardif, Jean-Claude
    Thorsteinsdottir, Unnur
    Tuomilehto, Jaako
    van Veldhuisen, Dirk J.
    Virtamo, Jarmo
    Viikari, Jorma
    Vollenweider, Peter
    Waeber, Gerard
    Widen, Elisabeth
    Cho, Yoon Shin
    Olsen, Jesper V.
    Visscher, Peter M.
    Willer, Cristen
    Franke, Lude
    Erdmann, Jeanette
    Thompson, John R.
    Pfeufer, Arne
    Sotoodehnia, Nona
    Newton-Cheh, Christopher
    Ellinor, Patrick T.
    Stricker, Bruno H. Ch
    Metspalu, Andres
    Perola, Markus
    Beckmann, Jacques S.
    Smith, George Davey
    Stefansson, Kari
    Wareham, Nicholas J.
    Munroe, Patricia B.
    Sibon, Ody C. M.
    Milan, David J.
    Snieder, Harold
    Samani, Nilesh J.
    Loos, Ruth J. F.
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 6, p. 621-+Article in journal (Refereed)
    Abstract [en]

    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

  • 12. den Hoed, Marcel
    et al.
    Hesselink, Matthijs K C
    van Kranenburg, Gerrit P J
    Westerterp, Klaas R
    Habitual physical activity in daily life correlates positively with markers for mitochondrial capacity.2008In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 105, no 2Article in journal (Refereed)
    Abstract [en]

    Physical exercise training is a powerful tool to maintain or improve mitochondrial density and function (mitochondrial capacity). This study aims to determine whether mitochondrial capacity is also associated with habitual physical activity in daily life (PADL). The capacity of classic markers for mitochondrial density, i.e., the capacity of citrate synthase (CS) and succinate dehydrogenase (SDH), as well the capacity of cytochrome c oxidase (COX) and beta-hydroxyacyl-CoA dehydrogenase (HAD), was determined in homogenized muscle biopsy samples obtained from the vastus lateralis muscle of nonexercising healthy young (age 20+/-2 yr) subjects (31 women, 7 men). PADL was measured during two periods of 14 days using a triaxial accelerometer for movement registration. CS, SDH, and COX were positively associated with PADL [P<0.05, R=0.36, 95% confidence interval (CI): 1.3.10(-4) to 2.2.10(-3); P<0.05, R=0.39, 95% CI: 1.1.10(-5) to 9.9.10(-5); and P<0.05, R=0.33, 95% CI: 7.5.10(-6) to 3.6.10(-4), respectively], and HAD tended to correlate positively with PADL (P=0.06, R=0.31, 95% CI: -2.2.10(-5) to 1.1.10(-3)). The population was subsequently stratified based on the intensity of the activities performed. CS was only associated with PADL in subjects spending more time on high-intensity physical activity, whereas HAD was only associated with PADL in subjects spending less time on low intensity physical activity. We are the first to report that even within the range of normal daily life activities, mitochondrial capacity is positively associated with the level of habitual physical activity in daily life. Thus an active lifestyle may help to maintain or improve mitochondrial capacity.

  • 13.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J
    Almgren, Peter
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engström, Gunnar
    de Faire, Ulf
    Hedblad, Bo
    Humphries, Steve E
    Lindgren, Cecilia M
    Morris, Andrew P
    Östling, Gerd
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Tremoli, Elena
    Hamsten, Anders
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melander, Olle
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 239, no 2, p. 304-310Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.

    OBJECTIVES: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.

    METHODS: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.

    RESULTS: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).

    CONCLUSIONS: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

  • 14. den Hoed, Marcel
    et al.
    Westerterp-Plantenga, Margriet S
    Bouwman, Freek G
    Mariman, Edwin C M
    Westerterp, Klaas R
    Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO.2009In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 90, no 5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The common rs9939609 single nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene is associated with adiposity, possibly by affecting satiety responsiveness.

    OBJECTIVE: The objective was to determine whether postprandial responses in hunger and satiety are associated with rs9939609, taking interactions with other relevant candidate genes into account.

    DESIGN: Sixty-two women and 41 men [age: 31 +/- 14 y; body mass index (in kg/m(2)): 25.0 +/- 3.1] were genotyped for 5 SNPs in FTO, DNMT1, DNMT3B, LEP, and LEPR. Individuals received fixed meals provided in energy balance. Hunger and satiety were determined pre- and postprandially by using visual analog scales.

    RESULTS: A general association test showed a significant association between postprandial responses in hunger and satiety with rs9939609 (P = 0.036 and P = 0.050, respectively). Individuals with low postprandial responses in hunger and satiety were overrepresented among TA/AA carriers in rs9939609 (FTO) compared with TT carriers (dominant and additive model: P = 0.013 and P = 0.020, respectively). Moreover, multifactor dimensionality reduction showed significant epistatic interactions for the postprandial decrease in hunger involving rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR). Individuals with a low postprandial decrease in hunger were overrepresented among TA/AA (dominant), CC/CA (recessive), and AG/GG (dominant) carriers in rs9939609 (FTO), rs992472 (DNMT3B), and rs1137101 (LEPR), respectively (n = 39), compared with TT, AA, and/or AA carriers in these SNPs, respectively (P = 0.00001). Each SNP had an additional effect.

    CONCLUSIONS: Our results confirm a role for FTO in responsiveness to hunger and satiety cues in adults in an experimental setting. The epistatic interaction suggests that DNA methylation, an epigenetic process, affects appetite.

  • 15. Elks, Cathy E
    et al.
    den Hoed, Marcel
    Zhao, Jing Hua
    Sharp, Stephen J
    Wareham, Nicholas J
    Loos, Ruth J F
    Ong, Ken K
    Variability in the heritability of body mass index: a systematic review and meta-regression.2012In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 3Article in journal (Refereed)
    Abstract [en]

    Evidence for a major role of genetic factors in the determination of body mass index (BMI) comes from studies of related individuals. Despite consistent evidence for a heritable component of BMI, estimates of BMI heritability vary widely between studies and the reasons for this remain unclear. While some variation is natural due to differences between populations and settings, study design factors may also explain some of the heterogeneity. We performed a systematic review that identified 88 independent estimates of BMI heritability from twin studies (total 140,525 twins) and 27 estimates from family studies (42,968 family members). BMI heritability estimates from twin studies ranged from 0.47 to 0.90 (5th/50th/95th centiles: 0.58/0.75/0.87) and were generally higher than those from family studies (range: 0.24-0.81; 5th/50th/95th centiles: 0.25/0.46/0.68). Meta-regression of the results from twin studies showed that BMI heritability estimates were 0.07 (P = 0.001) higher in children than in adults; estimates increased with mean age among childhood studies (+0.012/year, P = 0.002), but decreased with mean age in adult studies (-0.002/year, P = 0.002). Heritability estimates derived from AE twin models (which assume no contribution of shared environment) were 0.12 higher than those from ACE models (P < 0.001), whilst lower estimates were associated with self reported versus DNA-based determination of zygosity (-0.04, P = 0.02), and with self reported versus measured BMI (-0.05, P = 0.03). Although the observed differences in heritability according to aspects of study design are relatively small, together, the above factors explained 47% of the heterogeneity in estimates of BMI heritability from twin studies. In summary, while some variation in BMI heritability is expected due to population-level differences, study design factors explained nearly half the heterogeneity reported in twin studies. The genetic contribution to BMI appears to vary with age and may have a greater influence during childhood than adult life.

  • 16. Graff, Mariaelisa
    et al.
    Scott, Robert A
    Justice, Anne E
    Young, Kristin L
    Feitosa, Mary F
    Barata, Llilda
    Winkler, Thomas W
    Chu, Audrey Y
    Mahajan, Anubha
    Hadley, David
    Xue, Luting
    Workalemahu, Tsegaselassie
    Heard-Costa, Nancy L
    den Hoed, Marcel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Ahluwalia, Tarunveer S
    Qi, Qibin
    Ngwa, Julius S
    Renström, Frida
    Quaye, Lydia
    Eicher, John D
    Hayes, James E
    Cornelis, Marilyn
    Kutalik, Zoltan
    Lim, Elise
    Luan, Jian'an
    Huffman, Jennifer E
    Zhang, Weihua
    Zhao, Wei
    Griffin, Paula J
    Haller, Toomas
    Ahmad, Shafqat
    Marques-Vidal, Pedro M
    Bien, Stephanie
    Yengo, Loic
    Teumer, Alexander
    Smith, Albert Vernon
    Kumari, Meena
    Harder, Marie Neergaard
    Justesen, Johanne Marie
    Kleber, Marcus E
    Hollensted, Mette
    Lohman, Kurt
    Rivera, Natalia V
    Whitfield, John B
    Zhao, Jing Hua
    Stringham, Heather M
    Lyytikäinen, Leo-Pekka
    Huppertz, Charlotte
    Willemsen, Gonneke
    Peyrot, Wouter J
    Wu, Ying
    Kristiansson, Kati
    Demirkan, Ayse
    Fornage, Myriam
    Hassinen, Maija
    Bielak, Lawrence F
    Cadby, Gemma
    Tanaka, Toshiko
    Mägi, Reedik
    van der Most, Peter J
    Jackson, Anne U
    Bragg-Gresham, Jennifer L
    Vitart, Veronique
    Marten, Jonathan
    Navarro, Pau
    Bellis, Claire
    Pasko, Dorota
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Snitker, Søren
    Cheng, Yu-Ching
    Eriksson, Joel
    Lim, Unhee
    Aadahl, Mette
    Adair, Linda S
    Amin, Najaf
    Balkau, Beverley
    Auvinen, Juha
    Beilby, John
    Bergman, Richard N
    Bergmann, Sven
    Bertoni, Alain G
    Blangero, John
    Bonnefond, Amélie
    Bonnycastle, Lori L
    Borja, Judith B
    Brage, Søren
    Busonero, Fabio
    Buyske, Steve
    Campbell, Harry
    Chines, Peter S
    Collins, Francis S
    Corre, Tanguy
    Smith, George Davey
    Delgado, Graciela E
    Dueker, Nicole
    Dörr, Marcus
    Ebeling, Tapani
    Eiriksdottir, Gudny
    Esko, Tõnu
    Faul, Jessica D
    Fu, Mao
    Færch, Kristine
    Gieger, Christian
    Gläser, Sven
    Gong, Jian
    Gordon-Larsen, Penny
    Grallert, Harald
    Grammer, Tanja B
    Grarup, Niels
    van Grootheest, Gerard
    Harald, Kennet
    Hastie, Nicholas D
    Havulinna, Aki S
    Hernandez, Dena
    Hindorff, Lucia
    Hocking, Lynne J
    Holmens, Oddgeir L
    Holzapfel, Christina
    Hottenga, Jouke Jan
    Huang, Jie
    Huang, Tao
    Hui, Jennie
    Huth, Cornelia
    Hutri-Kähönen, Nina
    James, Alan L
    Jansson, John-Olov
    Jhun, Min A
    Juonala, Markus
    Kinnunen, Leena
    Koistinen, Heikki A
    Kolcic, Ivana
    Komulainen, Pirjo
    Kuusisto, Johanna
    Kvaløy, Kirsti
    Kähönen, Mika
    Lakka, Timo A
    Launer, Lenore J
    Lehne, Benjamin
    Lindgren, Cecilia M
    Lorentzon, Mattias
    Luben, Robert
    Marre, Michel
    Milaneschi, Yuri
    Monda, Keri L
    Montgomery, Grant W
    De Moor, Marleen H M
    Mulas, Antonella
    Müller-Nurasyid, Martina
    Musk, A W
    Männikkö, Reija
    Männistö, Satu
    Narisu, Narisu
    Nauck, Matthias
    Nettleton, Jennifer A
    Nolte, Ilja M
    Oldehinkel, Albertine J
    Olden, Matthias
    Ong, Ken K
    Padmanabhan, Sandosh
    Paternoster, Lavinia
    Perez, Jeremiah
    Perola, Markus
    Peters, Annette
    Peters, Ulrike
    Peyser, Patricia A
    Prokopenko, Inga
    Puolijoki, Hannu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rasmussen-Torvik, Laura J
    Rawal, Rajesh
    Ridker, Paul M
    Rose, Lynda M
    Rudan, Igor
    Sarti, Cinzia
    Sarzynski, Mark A
    Savonen, Kai
    Scott, William R
    Sanna, Serena
    Shuldiner, Alan R
    Sidney, Steve
    Silbernagel, Günther
    Smith, Blair H
    Smith, Jennifer A
    Snieder, Harold
    Stančáková, Alena
    Sternfeld, Barbara
    Swift, Amy J
    Tammelin, Tuija
    Tan, Sian-Tsung
    Thorand, Barbara
    Thuillier, Dorothée
    Vandenput, Liesbeth
    Vestergaard, Henrik
    van Vliet-Ostaptchouk, Jana V
    Vohl, Marie-Claude
    Völker, Uwe
    Waeber, Gérard
    Walker, Mark
    Wild, Sarah
    Wong, Andrew
    Wright, Alan F
    Zillikens, M Carola
    Zubair, Niha
    Haiman, Christopher A
    Lemarchand, Loic
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ohlsson, Claes
    Hofman, Albert
    Rivadeneira, Fernando
    Uitterlinden, André G
    Pérusse, Louis
    Wilson, James F
    Hayward, Caroline
    Polasek, Ozren
    Cucca, Francesco
    Hveem, Kristian
    Hartman, Catharina A
    Tönjes, Anke
    Bandinelli, Stefania
    Palmer, Lyle J
    Kardia, Sharon L R
    Rauramaa, Rainer
    Sørensen, Thorkild I A
    Tuomilehto, Jaakko
    Salomaa, Veikko
    Penninx, Brenda W J H
    de Geus, Eco J C
    Boomsma, Dorret I
    Lehtimäki, Terho
    Mangino, Massimo
    Laakso, Markku
    Bouchard, Claude
    Martin, Nicholas G
    Kuh, Diana
    Liu, Yongmei
    Linneberg, Allan
    März, Winfried
    Strauch, Konstantin
    Kivimäki, Mika
    Harris, Tamara B
    Gudnason, Vilmundur
    Völzke, Henry
    Qi, Lu
    Järvelin, Marjo-Riitta
    Chambers, John C
    Kooner, Jaspal S
    Froguel, Philippe
    Kooperberg, Charles
    Vollenweider, Peter
    Hallmans, Göran
    Hansen, Torben
    Pedersen, Oluf
    Metspalu, Andres
    Wareham, Nicholas J
    Langenberg, Claudia
    Weir, David R
    Porteous, David J
    Boerwinkle, Eric
    Chasman, Daniel I
    Abecasis, Gonçalo R
    Barroso, Inês
    McCarthy, Mark I
    Frayling, Timothy M
    O'Connell, Jeffrey R
    van Duijn, Cornelia M
    Boehnke, Michael
    Heid, Iris M
    Mohlke, Karen L
    Strachan, David P
    Fox, Caroline S
    Liu, Ching-Ti
    Hirschhorn, Joel N
    Klein, Robert J
    Johnson, Andrew D
    Borecki, Ingrid B
    Franks, Paul W
    North, Kari E
    Cupples, L Adrienne
    Loos, Ruth J F
    Kilpeläinen, Tuomas O
    Genome-wide physical activity interactions in adiposity: A meta-analysis of 200,452 adults.2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 4, article id e1006528Article in journal (Refereed)
    Abstract [en]

    Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

  • 17. Horikoshi, Momoko
    et al.
    Yaghootkar, Hanieh
    Mook-Kanamori, Dennis O
    Sovio, Ulla
    Taal, H Rob
    Hennig, Branwen J
    Bradfield, Jonathan P
    St Pourcain, Beate
    Evans, David M
    Charoen, Pimphen
    Kaakinen, Marika
    Cousminer, Diana L
    Lehtimäki, Terho
    Kreiner-Møller, Eskil
    Warrington, Nicole M
    Bustamante, Mariona
    Feenstra, Bjarke
    Berry, Diane J
    Thiering, Elisabeth
    Pfab, Thiemo
    Barton, Sheila J
    Shields, Beverley M
    Kerkhof, Marjan
    van Leeuwen, Elisabeth M
    Fulford, Anthony J
    Kutalik, Zoltán
    Zhao, Jing Hua
    den Hoed, Marcel
    Mahajan, Anubha
    Lindi, Virpi
    Goh, Liang-Kee
    Hottenga, Jouke-Jan
    Wu, Ying
    Raitakari, Olli T
    Harder, Marie N
    Meirhaeghe, Aline
    Ntalla, Ioanna
    Salem, Rany M
    Jameson, Karen A
    Zhou, Kaixin
    Monies, Dorota M
    Lagou, Vasiliki
    Kirin, Mirna
    Heikkinen, Jani
    Adair, Linda S
    Alkuraya, Fowzan S
    Al-Odaib, Ali
    Amouyel, Philippe
    Andersson, Ehm Astrid
    Bennett, Amanda J
    Blakemore, Alexandra I F
    Buxton, Jessica L
    Dallongeville, Jean
    Das, Shikta
    de Geus, Eco J C
    Estivill, Xavier
    Flexeder, Claudia
    Froguel, Philippe
    Geller, Frank
    Godfrey, Keith M
    Gottrand, Frédéric
    Groves, Christopher J
    Hansen, Torben
    Hirschhorn, Joel N
    Hofman, Albert
    Hollegaard, Mads V
    Hougaard, David M
    Hyppönen, Elina
    Inskip, Hazel M
    Isaacs, Aaron
    Jørgensen, Torben
    Kanaka-Gantenbein, Christina
    Kemp, John P
    Kiess, Wieland
    Kilpeläinen, Tuomas O
    Klopp, Norman
    Knight, Bridget A
    Kuzawa, Christopher W
    McMahon, George
    Newnham, John P
    Niinikoski, Harri
    Oostra, Ben A
    Pedersen, Louise
    Postma, Dirkje S
    Ring, Susan M
    Rivadeneira, Fernando
    Robertson, Neil R
    Sebert, Sylvain
    Simell, Olli
    Slowinski, Torsten
    Tiesler, Carla M T
    Tönjes, Anke
    Vaag, Allan
    Viikari, Jorma S
    Vink, Jacqueline M
    Vissing, Nadja Hawwa
    Wareham, Nicholas J
    Willemsen, Gonneke
    Witte, Daniel R
    Zhang, Haitao
    Zhao, Jianhua
    Wilson, James F
    Stumvoll, Michael
    Prentice, Andrew M
    Meyer, Brian F
    Pearson, Ewan R
    Boreham, Colin A G
    Cooper, Cyrus
    Gillman, Matthew W
    Dedoussis, George V
    Moreno, Luis A
    Pedersen, Oluf
    Saarinen, Maiju
    Mohlke, Karen L
    Boomsma, Dorret I
    Saw, Seang-Mei
    Lakka, Timo A
    Körner, Antje
    Loos, Ruth J F
    Ong, Ken K
    Vollenweider, Peter
    van Duijn, Cornelia M
    Koppelman, Gerard H
    Hattersley, Andrew T
    Holloway, John W
    Hocher, Berthold
    Heinrich, Joachim
    Power, Chris
    Melbye, Mads
    Guxens, Mònica
    Pennell, Craig E
    Bønnelykke, Klaus
    Bisgaard, Hans
    Eriksson, Johan G
    Widén, Elisabeth
    Hakonarson, Hakon
    Uitterlinden, André G
    Pouta, Anneli
    Lawlor, Debbie A
    Smith, George Davey
    Frayling, Timothy M
    McCarthy, Mark I
    Grant, Struan F A
    Jaddoe, Vincent W V
    Jarvelin, Marjo-Riitta
    Timpson, Nicholas J
    Prokopenko, Inga
    Freathy, Rachel M
    New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 1Article in journal (Refereed)
    Abstract [en]

    Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

  • 18. Kilpeläinen, Tuomas O
    et al.
    den Hoed, Marcel
    Ong, Ken K
    Grøntved, Anders
    Brage, Soren
    Jameson, Karen
    Cooper, Cyrus
    Khaw, Kay-Tee
    Ekelund, Ulf
    Wareham, Nicholas J
    Loos, Ruth J F
    Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals.2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 93, no 4Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background.

    OBJECTIVE: The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight.

    DESIGN: A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060); 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623); and 3) all published data (n(max) = 14,837).

    RESULTS: Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele; P = 0.012; n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele; P = 0.013; n = 28,219). These results were not significant after correction for multiple testing.

    CONCLUSIONS: Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.

  • 19.
    Kramer, Irene Fleur
    et al.
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Dept Surg, Div Trauma Surg, Maastricht, Netherlands..
    Snijders, Tim
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands..
    Smeets, Joey S. J.
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands..
    Leenders, Marika
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands..
    van Kranenburg, Janneau
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands..
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Maastricht Univ, Med Ctr, Dept Human Biol, Maastricht, Netherlands.
    Verdijk, Lex B.
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands..
    Poeze, Martijn
    Maastricht Univ, Med Ctr, Dept Surg, Div Trauma Surg, Maastricht, Netherlands..
    van Loon, Luc J. C.
    Maastricht Univ, Med Ctr, Dept Human Movement Sci, Maastricht, Netherlands..
    Extensive Type II Muscle Fiber Atrophy in Elderly Female Hip Fracture Patients2017In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 72, no 10, p. 1369-1375Article in journal (Refereed)
    Abstract [en]

    Background: Sarcopenia, or the loss of muscle mass and strength, is known to increase the risk for falls and (hip) fractures in older people. The objective of this study was to assess the skeletal muscle fiber characteristics in elderly female hip fracture patients.

    Method: Percutaneous needle biopsies were collected from the vastus lateralis muscle in 15 healthy young women (20 +/- 0.4 years), 15 healthy elderly women (79 +/- 1.7 years), and 15 elderly women with a fall-related hip fracture (82 +/- 1.5 years). Immunohistochemical analyses were performed to assess Type I and Type II muscle fiber size, and myonuclear and satellite cell content.

    Results: Type II muscle fiber size was significantly different between all groups (p <.05), with smaller Type II muscle fibers in the hip fracture patients (2,609 +/- 185 mu m(2)) compared with healthy elderly group (3,723 +/- 322 mu m(2)) and the largest Type II muscle fibers in the healthy young group (4,755 +/- 335 mu m(2)). Furthermore, Type I muscle fiber size was significantly lower in the hip fracture patients (4,684 +/- 211 mu m(2)) compared with the healthy elderly group (5,842 +/- 316 mu m(2), p =.02). The number of myonuclei per Type II muscle fiber was significantly lower in the healthy elderly and hip fracture group compared with the healthy young group (p =.011 and p =.002, respectively). Muscle fiber satellite cell content did not differ between groups.

    Conclusion: Elderly female hip fracture patients show extensive Type II muscle fiber atrophy when compared with healthy young or agematched healthy elderly controls. Type II muscle fiber atrophy is an important hallmark of sarcopenia and may predispose to falls and (hip) fractures in the older population.

  • 20.
    Lightfoot, J. Timothy
    et al.
    Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX USA;Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands.
    De Geus, Eco J. C.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
    Booth, Frank W.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Univ Missouri, Dept Nutr & Exercise Physiol, Columbia, MO USA;Univ Missouri, Dept Biomed Sci, Columbia, MO USA.
    Bray, Molly S.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Univ Texas Austin, Dept Nutr Sci, Austin, TX USA.
    den Hoed, Marcel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands.
    Kaprio, Jaakko
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland;Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland.
    Kelly, Scott A.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Ohio Wesleyan Univ, Dept Zool, Delaware, OH 43015 USA.
    Pomp, Daniel
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Saul, Michael C.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL USA.
    Thomis, Martine A.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Katholieke Univ Leuven, Dept Movement Sci, Fac Kinesiol & Rehabil Sci, Leuven, Belgium.
    Garland, Theodore, Jr.
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Univ Calif Riverside, Dept Evolut Ecol & Organismal Biol, Riverside, CA 92521 USA.
    Bouchard, Claude
    Vrije Univ Amsterdam, Genet & Biol Determinants Phys Act Consortium Gen, Amsterdam, Netherlands;Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
    Biological/Genetic Regulation of Physical Activity Level: Consensus From Genbiopac2018In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 50, no 4, p. 863-873Article, review/survey (Refereed)
    Abstract [en]

    Purpose: Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity.

    Conclusions: Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

  • 21.
    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 University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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 subtypes2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 4, p. 524-537Article in journal (Refereed)
    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.

  • 22. Nead, Kevin T.
    et al.
    Li, Aihua
    Wehner, Mackenzie R.
    Neupane, Binod
    Gustafsson, Stefan
    Butterworth, Adam
    Engert, James C.
    Davis, A. Darlene
    Hegele, Robert A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Miller, Ruby
    den Hoed, Marcel
    Khaw, Kay-Tee
    Kilpelaeinen, Tuomas O.
    Wareham, Nick
    Edwards, Todd L.
    Hallmans, Goeran
    Varga, Tibor V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kardia, Sharon L. R.
    Smith, Jennifer A.
    Zhao, Wei
    Faul, Jessica D.
    Weir, David
    Mi, Jie
    Xi, Bo
    Quinteros, Samuel Canizales
    Cooper, Cyrus
    Sayer, Avan Aihie
    Jameson, Karen
    Grontved, Anders
    Fornage, Myriam
    Sidney, Stephen
    Hanis, Craig L.
    Highland, Heather M.
    Haering, Hans-Ulrich
    Heni, Martin
    Lasky-Su, Jessica
    Weiss, Scott T.
    Gerhard, Glenn S.
    Still, Christopher
    Melka, Melkaey M.
    Pausova, Zdenka
    Paus, Tomas
    Grant, Struan F. A.
    Hakonarson, Hakon
    Price, R. Arlen
    Wang, Kai
    Scherag, Andre
    Hebebrand, Johannes
    Hinney, Anke
    Franks, Paul W.
    Frayling, Timothy M.
    McCarthy, Mark I.
    Hirschhorn, Joel N.
    Loos, Ruth J.
    Ingelsson, Erik
    Gerstein, Hertzel C.
    Yusuf, Salim
    Beyene, Joseph
    Anand, Sonia S.
    Meyre, David
    Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 12, p. 3582-3594Article in journal (Refereed)
    Abstract [en]

    Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) a parts per thousand yen 40 kg/m(2)], but their contribution to common obesity (BMI a parts per thousand yen 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 x 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 x 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (beta = 0.02, 95% CI 0.00-0.03; P = 5.57 x 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

  • 23.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, 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 University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, 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 risk2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 15805Article in journal (Refereed)
    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.

  • 24. Plasqui, G
    et al.
    den Hoed, M
    Bonomi, A
    Westerterp, K R
    Body composition in 10-13-year-old children: a comparison between air displacement plethysmography and deuterium dilution.2009In: International Journal of Pediatric Obesity, ISSN 1747-7166, E-ISSN 1747-7174, Vol. 4, no 4Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Air diplacement plethysmography (ADP) has become increasingly popular to assess body composition in children. The aim of this study was to compare ADP with deuterium dilution and to investigate the effect of using child-specific prediction equations to correct raw body volume from ADP for thoracic gas volume (TGV) and body surface area (BSA).

    METHODS: Thirty-seven healthy Dutch children (17 girls, 20 boys) aged 10-13 years were recruited. Body volume was measured using the Bod Pod. Both adult and child-specific prediction equations were used to correct raw body volume from the Bod Pod for TGV and BSA. Total body water (TBW) was assessed using deuterium dilution. Child-specific densities and hydration fractions of fat-free mass were used to convert body volume and TBW to percentage fat mass (%FM). Correlation and agreement between methods was assessed using linear regression analysis and Bland-Altman plots.

    RESULTS: Despite a high correlation between the Bod Pod and deuterium dilution (R=0.91, p <0.001), a significant difference was found between %FM obtained using the Bod Pod and deuterium dilution (p <0.001), regardless of the equation used to correct raw body volume for TGV and BSA. Bland-Altman plots showed a systematic bias towards a smaller difference between techniques at higher %FM.

    CONCLUSION: Significant differences in %FM were found between both methods. Given the underlying assumptions to translate body volume or TBW to %FM, it is recommended to use a 3- or 4-compartment model when assessing body composition in children.

  • 25. Richmond, Rebecca C.
    et al.
    Smith, George Davey
    Ness, Andy R.
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    McMahon, George
    Timpson, Nicholas J.
    Assessing Causality in the Association between Child Adiposity and Physical Activity Levels: A Mendelian Randomization Analysis2014In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 11, no 3Article in journal (Refereed)
    Abstract [en]

    Background Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects. Methods and Findings The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/m(2) (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6x10(-16)), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7x10(-29)), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0x10(-4)). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (similar to 5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI. Conclusions Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation. Please see later in the article for the Editors' Summary Editors' Summary Background The World Health Organization estimates that globally at least 42 million children under the age of five are obese. The World Health Organization recommends that all children undertake at least one hour of physical activity daily, on the basis that increased physical activity will reduce or prevent excessive weight gain in children and adolescents. In practice, while numerous studies have shown that body mass index (BMI) shows a strong inverse correlation with physical activity (i.e., active children are thinner than sedentary ones), exercise programs specifically targeted at obese children have had only very limited success in reducing weight. The reasons for this are not clear, although environmental factors such as watching television and lack of exercise facilities are traditionally blamed. Why Was This Study Done? ? One of the reasons why obese children do not lose weight through exercise might be that being fat in itself leads to a decrease in physical activity. This is termed reverse causation, i.e. , obesity causes sedentary behavior, rather than the other way around. The potential influence of environmental factors (e.g., lack of opportunity to exercise) makes it difficult to prove this argument. Recent research has demonstrated that specific genotypes are related to obesity in children. Specific variations within the DNA of individual genes (single nucleotide polymorphisms, or SNPs) are more common in obese individuals and predispose to greater adiposity across the weight distribution. While adiposity itself can be influenced by many environmental factors that complicate the interpretation of observed associations, at the population level, genetic variation is not related to the same factors, and over the life course cannot be changed. Investigations that exploit these properties of genetic associations to inform the interpretation of observed associations are termed Mendelian randomization studies. This research technique is used to reduce the influence of confounding environmental factors on an observed clinical condition. The authors of this study use Mendelian randomization to determine whether a genetic tendency towards high BMI and fat mass is correlated with reduced levels of physical activity in a large cohort of children. What Did the Researchers Do and Find? ? The researchers looked at a cohort of children from a large long-term health research project (the Avon Longitudinal Study of Parents and Children). BMI and total body fat were recorded. Total daily activity was measured via a small movement-counting device. In addition, the participants underwent genotyping to detect the presence of several SNPs known to be linked to obesity. For each child a total BMI allelic score was determined based on the number of obesity-related genetic variants carried by that individual. The association between obesity and reduced physical activity was then studied in two ways. Direct correlation between actual BMI and physical activity was measured (observational data). Separately, the link between BMI allelic score and physical activity was also determined (Mendelian randomization or instrumental variable analysis). The observational data showed that boys were more active than girls and had lower BMI. Across both sexes, a higher-than-average BMI was associated with lower daily activity. In genetic analyses, allelic score had a positive correlation with BMI, with one particular SNP being most strongly linked to high BMI and total fat mass. A high allelic score for BMI was also correlated with lower levels of daily physical activity. The authors conclude that children who are obese and have an inherent predisposition to high BMI also have a propensity to reduced levels of physical activity, which may compound their weight gain. What Do These Findings Mean? ? This study provides evidence that being fat is in itself a risk factor for low activity levels, separately from external environmental influences. This may be an example of "reverse causation," i.e., high BMI causes a reduction in physical activity. Alternatively, there may be a bidirectional causality, so that those with a genetic predisposition to high fat mass exercise less, leading to higher BMI, and so on, in a vicious circle. A significant limitation of the study is that validated allelic scores for physical activity are not available. Thus, it is not possible to determine whether individuals with a high allelic score for BMI also have a propensity to exercise less, or whether it is simply the circumstance of being overweight that discourages activity. This study does suggest that trying to persuade obese children to lose weight by exercising more is likely to be ineffective unless additional strategies to reduce BMI, such as strict diet control, are also implemented. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001618. The US Centers for Disease Control and Prevention provides obesity-related statistics, details of prevention programs, and an overview on public health strategy in the United States A more worldwide view is given by the World Health Organization The UK National Health Service website gives information on physical activity guidelines for different age groups The International Obesity Task Force is a network of organizations that seeks to alert the world to the growing health crisis threatened by soaring levels of obesity MedlinePlus-which brings together authoritative information from the US National Library of Medicine, National Institutes of Health, and other government agencies and health-related organizations-has a page on obesity Additional information on the Avon Longitudinal Study of Parents and Children is available The British Medical Journal has an article that describes <ext-link ext-link-type="uri" xlink:href="http://www.bmj.com/content/345/bmj. e7325" xlink:type="simple">Mendelian randomization

  • 26.
    Schoffelen, Paul F. M.
    et al.
    Maastricht Univ, Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Human Biol, Maastricht, Netherlands;Maastricht Univ, Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Nutr & Movement Sci, Maastricht, Netherlands.
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    van Breda, Eric
    Univ Antwerp, Dept Rehabil Sci & Physiotherapy, MOVANT, Fac Med & Hlth Sci, Antwerp, Belgium.
    Plasqui, Guy
    Maastricht Univ, Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Nutr & Movement Sci, Maastricht, Netherlands.
    Test-retest variability of VO2max using total-capture indirect calorimetry reveals linear relationship of VO2 and Power2019In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 29, no 2, p. 213-222Article in journal (Refereed)
    Abstract [en]

    This study aimed to analyze the intra-individual variation in VO2max of human subjects using total-capture and free-flow indirect calorimetry. Twenty-seven men (27 ± 5 year; VO2max 49-79 mL•kg-1 •min-1) performed two maximal exertion tests (CPETs) on a cycle ergometer, separated by a 7 ± 2 day interval. VO2 and VCO2 were assessed using an indirect calorimeter (Omnical) with total capture of exhalation in a free-flow airstream. Thirteen subjects performed a third maximal exertion test using a breath-by-breath calorimeter (Oxycon Pro). On-site validation was deemed a requirement. For the Omnical, the mean within-subject CV for VO2max was 1.2 ± 0.9% (0.0%-4.4%) and for ergometer workload P max 1.3 ± 1.3% (0%-4.6%). VO2max values with the Oxycon Pro were significantly lower in comparison with Omnical (P< t 0.001; t test) with mean 3570 vs 4061 and difference SD 361 mL • min-1. Validation results for the Omnical with methanol combustion were -0.05 ± 0.70% (mean ± SD; n = 31) at the 225 mL • min-1 VO2 level and -0.23 ± 0.80% (n = 31) at the 150 mL • min-1 VCO2 level. Results using gas infusion were 0.04 ± 0.75% (n = 34) and -0.99 ± 1.05% (n = 24) over the respective 500-6000 mL • min-1 VO2 and VCO2 ranges. Validation results for the Oxycon Pro in breath-by-breath mode were - 2.2 ± 1.6% (n = 12) for VO2 and 5.7 ± 3.3% (n = 12) for VCO2 over the 1000-4000 mL •min-1 range. On a Visual analog scale, participants reported improved breathing using the free-flow indirect calorimetry (score 7.6 ± 1.2 vs 5.1 ± 2.7, P = 0.008). We conclude that total capturing free-flow indirect calorimetry is suitable for measuring VO2 even with the highest range. VO2max was linear with the incline in P max over the full range.

  • 27. Soenen, Stijn
    et al.
    Mariman, Edwin C M
    Vogels, Neeltje
    Bouwman, Freek G
    den Hoed, Marcel
    Brown, Louise
    Westerterp-Plantenga, Margriet S
    Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance.2009In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 96, no 4-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Genetic variation in the perilipin (PLIN) gene may play a role in the etiology and treatment of obesity.

    OBJECTIVE: To examine different polymorphisms in the PLIN gene in relation to body-weight regulation.

    METHODS: 118 subjects followed a 6 wk VLCD, followed by 1 year weight maintenance. Body-weight (BW), body composition, leptin concentration, and polymorphisms of the PLIN gene: PLIN1:rs2289487, PLIN4:rs894160, PLIN6:rs1052700, PLIN5:rs2304795 and PLIN7:rs 2304796 were determined.

    RESULTS: BW loss during VLCD was 7.0+/-3.1 kg (p<0.05), and BW regain was 3.7+/-1.4 kg (p<0.05), including changes in body mass index (BMI), waist-circumference, body-composition and leptin concentrations (p<0.05). Linkage disequilibria were observed between PLIN1 and PLIN4: D' >0.9, r2=0.72; PLIN5 and PLIN7: D' >0.9, r2=0.85. In men, body weight, BMI, waist circumference, body fat, leptin concentrations were significantly lower for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). In women weight loss and loss of fat mass were larger for the haplotype of PLIN1 (C-alleles) and PLIN4 (A-alleles). For PLIN6 genotypes body weight and body fat were lower for homozygotes of the minor allele (T/T) in the men; in the women leptin concentrations were lower. The haplotype of PLIN5 and PLIN7 consisting of A/G and G/G of PLIN5 and A/A of PLIN7 showed a reduction in FM: 5.9+/-0.6 kg vs 3.1+/-0.4 kg, % body fat: 5.5+/-0.6% vs 2.2+/-0.2%, and leptin: 20.5+/-10.8 ng/ml vs 12.9+/-6.7 ng/ml over time in the women (p<0.05).

    CONCLUSION: Since the haplotype of the minor alleles PLIN1-4, PLIN5-7 and PLIN6, was related to body-weight regulation at a lower level of body-weight in the men as well in the women we conclude that the PLIN1-4, 6, and 5-7 locus appears as a genetic influencer of obesity risk in humans.

  • 28.
    Strawbridge, Rona J.
    et al.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Univ Glasgow, Inst Mental Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow, Lanark, Scotland.;Univ Glasgow, Dept Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland..
    Silveira, Angela
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Rybin, Denis
    Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Li-Gao, Ruifang
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands..
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Dehghan, Abbas
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Haljas, Kadri
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland..
    Lahti, Jari
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Gadin, Jesper R.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Backlund, Alexandra
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Giral, Phillipe
    Grp Hosp Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lindgren, Cecilia C. M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mannarino, Elmo
    Univ Perugia, Dept Clin & Expt Med Internal Med Angiol & Arteri, Perugia, Italy..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    de Mutsert, Renee
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Saliba-Gustafsson, Peter
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Sennblad, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Smit, Andries J.
    Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Bjorck, Hanna M.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Hofman, Albert
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Franco, Oscar H.
    Watkins, Hugh
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Florez, Jose C.
    Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA USA.;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Meigs, James B.
    Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA.;Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA..
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Baldassarre, Damiano
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy..
    Hamsten, Anders
    Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 266, p. 196-204Article in journal (Refereed)
    Abstract [en]

    Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.

    Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.

    Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.

    Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

  • 29.
    van Setten, Jessica
    et al.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands.
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Jamshidi, Yalda
    St Georges Univ London, Cardiogenet Lab, Mol & Clin Sci Res Inst, London SW17 0RE, England.
    Swenson, Brenton R.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Inst Publ Hlth Genet, Sch Publ Hlth, Seattle, WA 98195 USA.
    Butler, Anne M.
    Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh EH8 9YL, Midlothian, Scotland.
    Del Greco, Fabiola M.
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, I-39100 Bolzano, Italy.
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA.
    Gibson, Quince
    Univ Alabama Birmingham Hosp, Dept Surg, Birmingham, AL 35233 USA.
    Gudbjartsson, Daniel F.
    DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland;Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland.
    Kerr, Kathleen F.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
    Krijthe, Bouwe P.
    Erasmus MC, Dept Epidemiol, NL-3015 GD Rotterdam, Netherlands.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33014, Finland.
    Mueller, Christian
    Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20251 Hamburg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany.
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany;Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, D-81377 Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany;Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713GZ Groningen, Netherlands.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713GZ Groningen, Netherlands.
    Padmanabhan, Sandosh
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Ritchie, Marylyn D.
    Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Health, I-34137 Trieste, Italy.
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland;Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
    Steri, Maristella
    CNR, Ist Ric Genet & Biomed, I-00185 Cagliari, Italy.
    Tanaka, Toshiko
    NIA, Translat Gerontol Branch, Bethesda, MD 20892 USA.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands.
    Ulivi, Sheila
    IRCCS Burlo Garofolo, Inst Maternal & Child Health, I-34137 Trieste, Italy.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-7913GZ Groningen, Netherlands.
    Yin, Xiaoyan
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
    Arnar, David O.
    DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland;Landspitali Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland.
    Asselbergs, Folkert W.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands;Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London WC1E 6BT, England;UCL, Farr Inst Hlth Informat Res, London WC1E 6BT, England;UCL, Inst Hlth Informat, London WC1E 6BT, England.
    Bader, Joel S.
    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
    Barnard, John
    Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
    Bis, Josh
    Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20251 Hamburg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany.
    Blankenberg, Stefan
    DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Bradford, Yuki
    Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
    Buckley, Brendan M.
    Univ Coll Cork, Dept Pharmacol & Therapeut, Cork T12 K8AF, Ireland.
    Chung, Mina K.
    Cleveland Clin, Heart & Vasc Inst, Dept Cardiovasc Med, Cleveland, OH 44195 USA;Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA.
    Crawford, Dana
    Case Western Reserve Univ, Inst Computat Biol, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    den Hoed, Marcel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Denny, Josh C.
    Vanderbilt Univ, Biomed Informat & Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Dominiczak, Anna F.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Ehret, Georg B.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21287 USA.
    Eijgelsheim, Mark
    Erasmus MC, Dept Epidemiol, NL-3015 GD Rotterdam, Netherlands;Univ Med Ctr Groningen, Dept Nephrol, NL-7913GZ Groningen, Netherlands.
    Ellinor, Patrick T.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
    Felix, Stephan B.
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, D-17489 Greifswald, Germany.
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 GD Rotterdam, Netherlands.
    Franke, Lude
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
    Holm, Hilma
    DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.
    Ilaria, Gandin
    Univ Trieste, Dept Med Sci, I-34127 Trieste, Italy.
    Iorio, Annamaria
    Osped Riuniti, Cardiovasc Dept, I-34124 Trieste, Italy;Univ Trieste, I-34124 Trieste, Italy.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland;Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere 33014, Finland.
    Kolcic, Ivana
    Univ Split, Fac Med, Split 21000, Croatia.
    Kors, Jan A.
    Erasmus Univ, Med Ctr, Dept Med Informat, NL-3015 GD Rotterdam, Netherlands.
    Lakatta, Edward G.
    NIA, Lab Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
    Launer, Lenore J.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
    Lin, Henry J.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 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.
    Lubitz, Steven A.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
    Macfarlane, Peter W.
    Univ Glasgow, Inst Hlth & Wellbeing, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
    Magnani, Jared W.
    Univ Pittsburgh, Med Ctr, Heart & Vasc Inst, Dept Med,Div Cardiol, Pittsburgh, PA 15260 USA.
    Leach, Irene Mateo
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-7913GZ Groningen, Netherlands.
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany;Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
    Mitchell, Braxton D.
    Univ Maryland, Geriatr Res & Educ Clin Ctr, Baltimore VA Med Ctr, Dept Med,Sch Med, Baltimore, MD 21201 USA.
    Munzel, Thomas
    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, D-55131 Mainz, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Rhine Main, D-55131 Mainz, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, CTVB, D-55131 Mainz, Germany.
    Papanicolaou, George J.
    NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany;German Ctr Diabet Res, D-85764 Neuherberg, Germany.
    Pfeufer, Arne
    MVZ Molekulardiagnost, D-81543 Munich, Germany.
    Pramstaller, Peter P.
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, I-39100 Bolzano, Italy;Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy.
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20014, Finland.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 USA;Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Med, Torrance, CA 90502 USA.
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh EH8 9YL, Midlothian, Scotland.
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England;NIHR Leicester Biomed Res Ctr, Leicester LE3 9QD, Leics, England.
    Schlessinger, David
    NIA, Lab Genet & Gen, NIH, Baltimore, MD 20892 USA.
    Aldana, Claudia T. Silva
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GD Rotterdam, Netherlands;Univ Rosario, Sch Med & Hlth Sci, Ctr Res Genet & Genom CIGGUR, GENIUROS Res Grp,Inst Translat Med IMT, Cl 12c 6-25, Bogota, Colombia.
    Sinner, Moritz F.
    Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, D-81377 Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany.
    Smith, Jonathan D.
    Cleveland Clin, Heart & Vasc Inst, Dept Cardiovasc Med, Cleveland, OH 44195 USA;Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med Biol, Cleveland, OH 44195 USA.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713GZ Groningen, Netherlands.
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC 27101 USA.
    Spector, Timothy D.
    Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
    Stott, David J.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, D-81377 Munich, Germany.
    Tarasov, Kirill V.
    NIA, Lab Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
    Thorsteinsdottir, Unnur
    DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands.
    Van Wagoner, David R.
    Cleveland Clin, Heart & Vasc Inst, Dept Cardiovasc Med, Cleveland, OH 44195 USA.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17489 Greifswald, Germany.
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Waldenberger, Melanie
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
    Westra, Harm Jan
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands.
    Wild, Philipp S.
    DZHK German Ctr Cardiovasc Res, Partner Site Rhine Main, D-55131 Mainz, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, CTVB, D-55131 Mainz, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, Prevent Cardiol & Prevent Med, D-55131 Mainz, Germany;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55131 Mainz, Germany.
    Zeller, Tanja
    Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20251 Hamburg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany.
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
    Avery, Christy L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA;Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27514 USA.
    Bandinelli, Stefania
    ASF, Geriatr Unit, I-50122 Florence, Italy.
    Benjamin, Emelia J.
    Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Cucca, Francesco
    CNR, Ist Ric Genet & Biomed, I-00185 Cagliari, Italy.
    Doerr, Marcus
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, D-17489 Greifswald, Germany.
    Ferrucci, Luigi
    NIA, Translat Gerontol Branch, Bethesda, MD 20892 USA.
    Gasparini, Paolo
    IRCCS Burlo Garofolo, Inst Maternal & Child Health, I-34137 Trieste, Italy;Univ Trieste, Dept Med Sci, I-34127 Trieste, Italy.
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh EH8 9YL, Midlothian, Scotland.
    Heckbert, Susan R.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
    Hicks, Andrew A.
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, I-39100 Bolzano, Italy.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands;Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2300 RC Leiden, Netherlands;Interuniv Cardiol Inst Netherlands, NL-3511EP Utrecht, Netherlands.
    Kaeaeb, Stefan
    Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, D-81377 Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33014, Finland.
    Liu, Yongmei
    Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27101 USA.
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London E1 4NS, England;Barts Hlth NHS Trust & Queen Mary Univ London, NIHR Biomed Res Ctr, London E1 4NS, England.
    Parsa, Afshin
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA;Baltimore VA Med Ctr, Baltimore, MD 21201 USA.
    Polasek, Ozren
    Univ Split, Fac Med, Split 21000, Croatia;Psychiat Hosp Sveti Ivan, Zagreb 10000, Croatia;Gen Info Ltd, Zagreb 10000, Croatia.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA.
    Roden, Dan M.
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland;Vanderbilt Univ, Med Pharmacol & Biomed Informat, Nashville, TN 37235 USA.
    Schnabel, Renate B.
    Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20251 Hamburg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany.
    Sinagra, Gianfranco
    Osped Riuniti, Cardiovasc Dept, I-34124 Trieste, Italy;Univ Trieste, I-34124 Trieste, Italy.
    Stefansson, Kari
    DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
    Stricker, Bruno H.
    Erasmus MC, Dept Epidemiol, NL-3015 GD Rotterdam, Netherlands;Erasmus MC, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands;Inspectorate Hlth Care, NL-2511VX The Hague, Netherlands.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-7913GZ Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands;Netherlands Heart Inst, ICIN, Durrer Ctr Cardiogenet Res, NL-3511EP Utrecht, Netherlands.
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GD Rotterdam, Netherlands.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh EH8 9YL, Midlothian, Scotland.
    Gharib, Sina A.
    Univ Washington, Div Pulm Crit Care & Sleep Med, Computat Med Core Ctr Lung Biol, Cardiovasc Hlth Res Unit,Dept Med, Seattle, WA 98195 USA.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, NL-3584 CX Utrecht, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands.
    Isaacs, Aaron
    CARIM Sch Cardiovasc Dis, NL-6229ER Maastricht, Netherlands;Maastricht Univ, Ctr Syst Biol MaCSBio, NL-6229ER Maastricht, Netherlands;Maastricht Univ, Dept Biochem, NL-6229ER Maastricht, Netherlands.
    Arking, Dan E.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA.
    Sotoodehnia, Nona
    Univ Washington, Cardiovasc Hlth Res Unit, Div Cardiol, Dept Med, Seattle, WA 98101 USA;Univ Washington, Cardiovasc Hlth Res Unit, Div Cardiol, Dept Epidemiol, Seattle, WA 98101 USA.
    PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 2904Article in journal (Refereed)
    Abstract [en]

    Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

  • 30. van Vliet-Ostaptchouk, J. V.
    et al.
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Luan, J.
    Zhao, J.
    Ong, K.
    Wong, A.
    Hardy, R.
    Kuh, D.
    Van der Klauw, M.
    Bruinenberg, M.
    Khaw, K. -T
    Wolffenbuttel, B.
    Wareham, N.
    Snieder, H.
    Loos, R.
    Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 1, p. S158-S158Article in journal (Other academic)
1 - 30 of 30
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