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Research Article

A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels

  • J. Brent Richards mail,

    brent.richards@mcgill.ca

    Affiliations: Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montréal, Québec, Canada, Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

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  • Dawn Waterworth,

    Affiliation: Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America

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  • Stephen O'Rahilly,

    Affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom

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  • Marie-France Hivert,

    Affiliations: General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Ruth J. F. Loos,

    Affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom

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  • John R. B. Perry,

    Affiliations: Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom, Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom

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  • Toshiko Tanaka,

    Affiliations: Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America, Medstar Research Institute, Baltimore, Maryland, United States of America

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  • Nicholas John Timpson,

    Affiliation: Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Oakfield House, Bristol, United Kingdom

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  • Robert K. Semple,

    Affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom

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  • Nicole Soranzo,

    Affiliations: Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom

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  • Kijoung Song,

    Affiliation: Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America

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  • Nuno Rocha,

    Affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom

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  • Elin Grundberg,

    Affiliations: Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montréal, Québec, Canada, McGill University and Genome Québec Innovation Center, Montréal, Québec, Canada

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  • Josée Dupuis,

    Affiliation: Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States of America

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  • Jose C. Florez,

    Affiliations: Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America, Center for Human, Genetic Research and Diabetes Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Claudia Langenberg,

    Affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom

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  • Inga Prokopenko,

    Affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

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  • Richa Saxena,

    Affiliations: Center for Human, Genetic Research and Diabetes Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Robert Sladek,

    Affiliation: Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montréal, Québec, Canada

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  • Yurii Aulchenko,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

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  • David Evans,

    Affiliation: Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Oakfield House, Bristol, United Kingdom

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  • Gerard Waeber,

    Affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) University Hospital, Lausanne, Switzerland

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  • Jeanette Erdmann,

    Affiliation: Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany

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  • Mary-Susan Burnett,

    Affiliation: Cardiovascular Research Institute, Washington Hospital Center, Washington, District of Columbia, United States of America

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  • Naveed Sattar,

    Affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom

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  • Joseph Devaney,

    Affiliation: Cardiovascular Research Institute, Washington Hospital Center, Washington, District of Columbia, United States of America

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  • Christina Willenborg,

    Affiliations: Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany, Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany

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  • Aroon Hingorani,

    Affiliation: Centre for Clinical Pharmacology, University College, London, United Kingdom

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  • Jaquelin C. M. Witteman,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

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  • Peter Vollenweider,

    Affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) University Hospital, Lausanne, Switzerland

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  • Beate Glaser,

    Affiliation: Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Oakfield House, Bristol, United Kingdom

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  • Christian Hengstenberg,

    Affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

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  • Luigi Ferrucci,

    Affiliation: Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America

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  • David Melzer,

    Affiliation: Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom

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  • Klaus Stark,

    Affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

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  • John Deanfield,

    Affiliation: Cardiothoracic Unit, Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom

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  • Janina Winogradow,

    Affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

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  • Martina Grassl,

    Affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

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  • Alistair S. Hall,

    Affiliation: Leeds Institute of Genetics, Health and Therapeutics and Leeds Institute of Molecular Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom

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  • Josephine M. Egan,

    Affiliation: Laboratory of Clinical Investigation, National Institute of Aging, Baltimore, Maryland, United States of America

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  • John R. Thompson,

    Affiliation: Departments of Health Sciences, University of Leicester, Leicester, United Kingdom

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  • Sally L. Ricketts,

    Affiliation: Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom

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  • Inke R. König,

    Affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany

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  • Wibke Reinhard,

    Affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany

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  • Scott Grundy,

    Affiliation: Center for Human Nutrition, Department of Clinical Nutrition, University of Texas, Southwestern Medical Center, Dallas, Texas, United States of America

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  • H-Erich Wichmann,

    Affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Information Science, Biometry and Epidemiology, Ludwig-Maximilans-Universität, Munich, Germany

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  • Phil Barter,

    Affiliation: Heart Research Institute, Camperdown, Sydney, New South Wales, Australia

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  • Robert Mahley,

    Affiliation: Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, San Francisco, California, United States of America

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  • Y. Antero Kesaniemi,

    Affiliation: Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland

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  • Daniel J. Rader,

    Affiliation: Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America

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  • Muredach P. Reilly,

    Affiliation: Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America

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  • Stephen E. Epstein,

    Affiliation: Cardiovascular Research Institute, Washington Hospital Center, Washington, District of Columbia, United States of America

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  • Alexandre F. R. Stewart,

    Affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

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  • Cornelia M. Van Duijn,

    Affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands

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  • Heribert Schunkert,

    Affiliation: Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany

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  • Keith Burling,

    Affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom

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  • Panos Deloukas,

    Affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom

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  • Tomi Pastinen,

    Affiliations: Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montréal, Québec, Canada, McGill University and Genome Québec Innovation Center, Montréal, Québec, Canada

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  • Nilesh J. Samani,

    Affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom

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  • Ruth McPherson,

    Affiliation: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

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  • George Davey Smith,

    Affiliation: Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Oakfield House, Bristol, United Kingdom

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  • Timothy M. Frayling,

    Affiliations: Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom, Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom

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  • Nicholas J. Wareham,

    Affiliation: Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom

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  • James B. Meigs,

    Affiliations: General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Vincent Mooser equal contributor,

    equal contributor Contributed equally to this work with: Vincent Mooser, Tim D. Spector

    Affiliation: Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America

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  • Tim D. Spector equal contributor,

    equal contributor Contributed equally to this work with: Vincent Mooser, Tim D. Spector

    Affiliation: Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

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  • GIANT Consortium
  • Published: December 11, 2009
  • DOI: 10.1371/journal.pgen.1000768

About the Authors

J. Brent Richards, Elin Grundberg, Robert Sladek, Tomi Pastinen
Departments of Medicine, Human Genetics, and Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montréal, Québec, Canada
J. Brent Richards, Nicole Soranzo, Tim D. Spector
Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
Dawn Waterworth, Kijoung Song, Vincent Mooser
Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, United States of America
Stephen O'Rahilly, Robert K. Semple, Nuno Rocha, Keith Burling
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom
Marie-France Hivert, James B. Meigs
General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Marie-France Hivert, Jose C. Florez, James B. Meigs
Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America
Ruth J. F. Loos, Claudia Langenberg, Nicholas J. Wareham
Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom
John R. B. Perry, David Melzer, Timothy M. Frayling
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
John R. B. Perry, Timothy M. Frayling
Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
Toshiko Tanaka, Luigi Ferrucci
Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America
Toshiko Tanaka
Medstar Research Institute, Baltimore, Maryland, United States of America
Nicholas John Timpson, David Evans, Beate Glaser, George Davey Smith
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Oakfield House, Bristol, United Kingdom
Nicole Soranzo, Panos Deloukas
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom
Elin Grundberg, Tomi Pastinen
McGill University and Genome Québec Innovation Center, Montréal, Québec, Canada
Josée Dupuis
Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, United States of America
Jose C. Florez, Richa Saxena
Center for Human, Genetic Research and Diabetes Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Jose C. Florez, Richa Saxena
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
Inga Prokopenko
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
Yurii Aulchenko, Jaquelin C. M. Witteman, Cornelia M. Van Duijn
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
Gerard Waeber, Peter Vollenweider
Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) University Hospital, Lausanne, Switzerland
Jeanette Erdmann, Christina Willenborg, Heribert Schunkert
Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany
Mary-Susan Burnett, Joseph Devaney, Stephen E. Epstein
Cardiovascular Research Institute, Washington Hospital Center, Washington, District of Columbia, United States of America
Naveed Sattar
British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom
Christina Willenborg, Inke R. König
Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany
Aroon Hingorani
Centre for Clinical Pharmacology, University College, London, United Kingdom
Christian Hengstenberg, Klaus Stark, Janina Winogradow, Martina Grassl, Wibke Reinhard
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany
John Deanfield
Cardiothoracic Unit, Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom
Alistair S. Hall
Leeds Institute of Genetics, Health and Therapeutics and Leeds Institute of Molecular Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
Josephine M. Egan
Laboratory of Clinical Investigation, National Institute of Aging, Baltimore, Maryland, United States of America
John R. Thompson
Departments of Health Sciences, University of Leicester, Leicester, United Kingdom
Sally L. Ricketts
Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom
Scott Grundy
Center for Human Nutrition, Department of Clinical Nutrition, University of Texas, Southwestern Medical Center, Dallas, Texas, United States of America
H-Erich Wichmann
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Information Science, Biometry and Epidemiology, Ludwig-Maximilans-Universität, Munich, Germany
Phil Barter
Heart Research Institute, Camperdown, Sydney, New South Wales, Australia
Robert Mahley
Gladstone Institute of Neurological Disease and Gladstone Institute of Cardiovascular Disease, San Francisco, California, United States of America
Y. Antero Kesaniemi
Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
Daniel J. Rader, Muredach P. Reilly
Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
Alexandre F. R. Stewart, Ruth McPherson
Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
Nilesh J. Samani
Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United Kingdom

Corresponding Author

Email: brent.richards@mcgill.ca

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Ran meta-analysis: J. B. Richards, K. Song. Ran statistical analysis in studies: J. B. Richards, D. Waterworth, M.-F. Hivert, R. J. F. Loos, J. R. B. Perry, T. Tanaka, N. J. Timpson, K. Song, C. Langenberg, I. Prokopenko, R. Saxena, Y. Aluchenko, D. Evans, J. Erdmann, C. Willenborg, J. C. M. Witteman, B. Glaser, I. R. König, C. M. Van Duijn, T. M. Frayling. Designed studies: J. B. Richards, D. Waterworth, J. Dupuis, J. C. Florez, G. Waeber, J. Erdmann, M.-S. Burnett, J. Devaney, P. Vollenweider, C. Hengstenberg, L. Ferruci, D. Melzer, K. Stark, J. Deanfield, A. S. Hall, J. M. Egan, S. Grundy, P. Barter, Y. A. Kesaniemi, D. J. Rader, M. P. Reilly, S. E. Epstein, A. F. R. Stewart, N. J. Samani, R. McPherson, N. J. Wareham, J. B. Weigs, V. Mooser, T. D. Spector. Established the consortium: J. B. Richards, D. Waterworth, C. Hengstenberg, V. Mooser, T. D. Spector. Interpreted results and critically read the manuscript: J. B. Richards, D. Waterworth, S. O'Rahilly, M.-F. Hivert, R. J. F. Loos, J. R. B. Perry, T. Tanaka, N. J. Timpson, R. K. Semple, N. Soranzo, K. Song, N. Rocha, E. Grundberg, J. Dupuis, J. C. Florez, C. Langenberg, I. Prokopenko, R. Saxena, R. Sladek, Y. Aluchenko, D. Evans, G. Waeber, J. Erdmann, M.-S. Burnett, N. Sattar, J. Devaney, C. Willenborg, A. Hingorani, J. C. M. Witteman, P. Vollenweider, B. Glaser, C. Hengstenberg, L. Ferruci, D. Melzer, K. Stark, J. Deanfield, J. Winogradow, M. Grassl, A. S. Hall, J. M. Egan, J. R. Thompson, S. L. Ricketts, I. R. König, W. Reinhard, S. Grundy, H. E. Wichmann, P. Barter, R. Mahley, Y. A. Kesaniemi, D. J. Rader, M. P. Reilly, S. E. Epstein, A. F. R. Stewart, C. M. Van Duijn, H. Schunkert, K. Burling, P. Deloukas, T. Pastinen, N. J. Samani, R. McPherson, G. Davey Smith, T. M. Frayling, N. J. Wareham, J. B. Weigs, V. Mooser, T. D. Spector. Wrote the first draft of the manuscript: J. B. Richards. Coordinated/collected phenotypic information: D. W, G. Waeber, M.-S. Burnett, N. Sattar, J. Devaney, A. Hingorani, P. Vollenweider, C. Hengstenberg, K. Stark, J. Winogradow, M. Grassl, A. S. Hall, S. L. Ricketts, W. Reinhard, S. Grundy, H. E. Wichmann, P. Barter, R. Mahley, Y. A. Kesaniemi, D. J. Rader, M. P. Reilly, S. E. Epstein, N. J. Samani, R. McPherson, G. Davey Smith, J. B. Weigs, V. Mooser, T. D. Spector. Performed expression studies: S. O'Rahilly, R. K. Semple, N. Rocha, E. Grundberg, T. Pastinen. Coordinated GWA genotyping of studies: N. Soranzo, J. Erdmann, C. Hengstenberg, K. Stark, M. P. Reilly, H. Schunkert, P. Deloukas, T. D. Spector. Obtained funding: J. Dupuis, J. C. Florez, J. Erdmann, N. Sattar, C. Hengstenberg, A. S. Hall, J. M. Egan, J. R. Thompson, D. J. Rader, M. P. Reilly, S. E. Epstein, A. F. R. Stewart, N. J. Samani, R. McPherson, G. Davey Smith, N. J. Wareham, J. B. Weigs, T. D. Spector. Performed laboratory analyses: N. Sattar, K. Stark, J. M. Egan, K. Burling, R. McPherson. Provided data for the BMI trait: GIANT Consortium.