Article | Published:

Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders

Nature Genetics volume 45, pages 621631 (2013) | Download Citation

Abstract

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.

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Acknowledgements

A full list of acknowledgments appears in the Supplementary Note. Funding sources had no involvement in the collection, analysis and interpretation of the data.

Author information

Affiliations

  1. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Marcel den Hoed
    • , Jing Hua Zhao
    • , Jian'an Luan
    • , Søren Brage
    • , Claudia Langenberg
    • , Ken K Ong
    • , Robert A Scott
    • , Stephen Sharp
    • , Ulf Ekelund
    • , Nita G Forouhi
    • , Nicholas J Wareham
    •  & Ruth J F Loos
  2. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

    • Marcel den Hoed
    •  & Erik Ingelsson
  3. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Mark Eijgelsheim
    • , Aaron Isaacs
    • , Albert Hofman
    • , André G Uitterlinden
    • , Jacqueline C M Witteman
    • , Cornelia M van Duijn
    •  & Bruno H Ch Stricker
  4. Estonian Biocenter, Tartu, Estonia.

    • Tõnu Esko
    • , Evelin Mihailov
    • , Mari Nelis
    •  & Andres Metspalu
  5. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Krista Fischer
    • , Lili Milani
    • , Mari Nelis
    • , Andres Metspalu
    •  & Markus Perola
  6. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Evelin Mihailov
    •  & Andres Metspalu
  7. Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Bianca J J M Brundel
    •  & Femke Hoogstra-Berends
  8. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • David S Peal
    • , Stacey N Lynch
    • , Jordan T Shin
    •  & David J Milan
  9. MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE), School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • David M Evans
    • , John P Kemp
    • , Beate St. Pourcain
    • , Nicholas J Timpson
    •  & George Davey Smith
  10. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Ilja M Nolte
    • , Ronald P Stolk
    •  & Harold Snieder
  11. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Ayellet V Segrè
  12. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Ayellet V Segrè
    • , Robert E Handsaker
    • , Paul I W de Bakker
    • , Steven A McCarroll
    •  & Christopher Newton-Cheh
  13. deCODE Genetics, Reykjavik, Iceland.

    • Hilma Holm
    • , Daniel Gudbjartsson
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  14. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Robert E Handsaker
    •  & Steven A McCarroll
  15. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Harm-Jan Westra
    • , Cisca Wijmenga
    •  & Lude Franke
  16. Clinical Pharmacology, National Institute for Health Research (NIHR) Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Toby Johnson
    • , W L Mark Caulfield
    •  & Patricia B Munroe
  17. Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Toby Johnson
    • , W L Mark Caulfield
    •  & Patricia B Munroe
  18. Centre for Medical Systems Biology, Leiden, The Netherlands.

    • Aaron Isaacs
    •  & Cornelia M van Duijn
  19. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • Jian Yang
    •  & Nicole Soranzo
  20. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Alicia Lundby
    • , Sarah E Medland
    • , Elizabeth J Rossin
    •  & Chip Stewart
  21. The Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark.

  22. Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Jesper V Olsen
  23. Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Daejeon, The Republic of Korea.

    • Young Jin Kim
    •  & Min Jin Go
  24. Department of Clinical Sciences, Diabetes and Endocrinology, Lund University and Lund University Diabetes Centre, Malmö, Sweden.

    • Peter Almgren
    • , Claes Ladenvall
    •  & Leif Groop
  25. Community Prevention Unit, Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.

    • Murielle Bochud
  26. Université de Montréal, Montreal, Quebec, Canada.

    • Gabrielle Boucher
    • , Philippe Goyette
    • , John D Rioux
    •  & Jean-Claude Tardif
  27. Montreal Heart Institute, Montreal, Quebec, Canada.

    • Gabrielle Boucher
    • , Philippe Goyette
    • , John D Rioux
    •  & Jean-Claude Tardif
  28. Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Marilyn C Cornelis
    • , Majken K Jensen
    • , Frank B Hu
    • , Lu Qi
    •  & Eric B Rimm
  29. Division of Population Health Sciences and Education, St. George's, University of London, London, UK.

    • David Hadley
    •  & David P Strachan
  30. Pediatric Epidemiology Center, University of South Florida, Tampa, Florida, USA.

    • David Hadley
  31. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Pim van der Harst
    • , Irene Mateo Leach
    • , Rudolf A de Boer
    • , Wiek H van Gilst
    •  & Dirk J van Veldhuisen
  32. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

    • Caroline Hayward
    • , Veronique Vitart
    •  & Pau Navarro
  33. Department of Internal Medicine, VU Medical Center, Amsterdam, The Netherlands.

    • Martin den Heijer
  34. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

    • Wilmar Igl
    • , Åsa Johansson
    •  & Ulf Gyllensten
  35. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

    • Anne U Jackson
    • , Christian Fuchsberger
    • , Heather M Stringham
    •  & Michael Boehnke
  36. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Anne U Jackson
    • , Heather M Stringham
    •  & Michael Boehnke
  37. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Zoltán Kutalik
    • , Paola Benaglio
    •  & Jacques S Beckmann
  38. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Zoltán Kutalik
  39. The Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.

    • Kati Kristiansson
    • , Perttu Salo
    •  & Markus Perola
  40. Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.

    • Kati Kristiansson
  41. Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

    • Mattias Lorentzon
    • , Liesbeth Vandenput
    •  & Claes Ohlsson
  42. Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland, School of Medicine, Baltimore, Maryland, USA.

    • May E Montasser
    • , Jeffrey R O'Connell
    • , Braxton D Mitchell
    •  & Alan R Shuldiner
  43. Department of Medicine, Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.

    • Omer T Njajou
    •  & Wen-Chi Hsueh
  44. Department of Epidemiology and Biostatistics, Imperial College London, London, UK.

    • Paul F O'Reilly
    • , Weihua Zhang
    • , Paul Elliott
    • , Kathryn A Miller
    • , John C Chambers
    •  & Marjo-Riitta Jarvelin
  45. MRC–Health Protection Agency (MRC-HPA) Centre for Environment and Health, Imperial College London, London, UK.

    • Paul F O'Reilly
    • , Paul Elliott
    •  & Marjo-Riitta Jarvelin
  46. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

    • Sandosh Padmanabhan
  47. Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

    • Tuomo Rankinen
    •  & Claude Bouchard
  48. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Perttu Salo
    • , Aki S Havulinna
    • , Johan Eriksson
    • , Veikko Salomaa
    • , Jarmo Virtamo
    •  & Markus Perola
  49. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
    •  & Luigi Ferrucci
  50. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

    • Lindsay Waite
    •  & Devin Absher
  51. Information Management Services, Inc., Rockville, Maryland, USA.

    • William Wheeler
  52. Department of Biological Psychology, VU University Amsterdam and Institute for Health and Care Research (EMGO+), VU Medical Center, Amsterdam, The Netherlands.

    • Harmen H M Draisma
    • , Eco J C de Geus
    • , Jouke-Jan Hottenga
    • , Gonneke Willemsen
    •  & Dorret I Boomsma
  53. Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Mary F Feitosa
    • , Shamika Ketkar
    •  & Ingrid B Borecki
  54. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Kathleen F Kerr
    • , Quenna Wong
    •  & Richard A Kronmal
  55. Quantitative Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • Penelope A Lind
    •  & Sarah E Medland
  56. Complex Genetics Section, Department of Medical Genetics–de Bakker Group, University Medical Center Utrecht, Utrecht, The Netherlands.

    • N Charlotte Onland-Moret
  57. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

    • N Charlotte Onland-Moret
    • , Paul I W de Bakker
    • , Maarten Leusink
    •  & Yvonne T van der Schouw
  58. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Ci Song
    • , Erik Ingelsson
    •  & Nancy L Pedersen
  59. Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.

    • Michael N Weedon
    •  & Weijia Xie
  60. Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8199, Institut Pasteur de Lille, Lille, France.

    • Loic Yengo
    • , Nabila Bouatia-Naji
    •  & Philippe Froguel
  61. Division of Preventive Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Christine M Albert
  62. Harvard Medical School, Boston, Massachusetts, USA.

    • Christine M Albert
    •  & Patrick T Ellinor
  63. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • Alvaro Alonso
  64. Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Dan E Arking
  65. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Dan E Arking
  66. Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Paul I W de Bakker
  67. Department of Medical Genetics, Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.

    • Paul I W de Bakker
  68. Institut National de la Santé et de la Recherche Médicale (INSERM), CESP Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease over the Lifecourse, Villejuif, France.

    • Beverley Balkau
  69. UMRS 1018, Université Paris–Sud 11, Villejuif, France.

    • Beverley Balkau
  70. Department of Health Sciences, Milan University and Filarete Foundation, Milan, Italy.

    • Cristina Barlassina
    •  & Daniele Cusi
  71. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    • , Susan R Heckbert
    • , Bruce M Psaty
    •  & Nona Sotoodehnia
  72. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    •  & Bruce M Psaty
  73. Lille Nord de France University, Lille, France.

    • Nabila Bouatia-Naji
    •  & Philippe Froguel
  74. INSERM U970, Paris Cardiovascular Research Centre, Hopital Européen Georges Pampidou, Paris, France.

    • Nabila Bouatia-Naji
  75. Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, Maryland, USA.

    • Stephen J Chanock
    •  & Demetrius Albanes
  76. Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, Maryland, USA.

    • Stephen J Chanock
  77. National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Peter S Chines
  78. Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA.

    • Mina Chung
  79. Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

    • Mina Chung
  80. Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Dawood Darbar
  81. INSERM U1087, CNRS U6291 and University of Nantes, l'Institut du Thorax, Nantes, France.

    • Christian Dina
  82. Centre Hospitalier Universitaire (CHU) Nantes, l'Institut du Thorax, Nantes, France.

    • Christian Dina
  83. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.

    • Marcus Dörr
    •  & Stephan B Felix
  84. DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.

    • Marcus Dörr
    •  & Stephan B Felix
  85. Icelandic Heart Association Research Institute, Kopavogur, Iceland.

    • Vilmundur Gudnason
    •  & Albert V Smith
  86. University of Iceland, Reykjavik, Iceland.

    • Vilmundur Gudnason
  87. Laboratory for Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA.

    • Tamara B Harris
  88. Department of Clinical Sciences, Obstetrics and Gynecology, University of Oulu, Oulu, Finland.

    • Anna-Liisa Hartikainen
    •  & Anneli Pouta
  89. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Susan R Heckbert
    •  & Bruce M Psaty
  90. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated institute of the University of Lübeck).

    • Andrew A Hicks
    • , Peter P Pramstaller
    •  & Jeanette Erdmann
  91. Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Ageing, Rotterdam, The Netherlands.

    • Albert Hofman
    • , André G Uitterlinden
    • , Jacqueline C M Witteman
    •  & Bruno H Ch Stricker
  92. Department of General Internal Medicine, Division of Vascular Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    • Suzanne Holewijn
    •  & Jacqueline de Graaf
  93. Nyken, Groningen, The Netherlands.

    • Femke Hoogstra-Berends
  94. Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden.

    • Åsa Johansson
  95. Division of Cardiology, Miller School of Medicine, University of Miami, Miami, Florida, USA.

    • Juhani Junttila
  96. Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland.

    • Juhani Junttila
    •  & Heikki V Huikuri
  97. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians- Universität, Munich, Germany.

    • Stefan Kääb
    •  & Martina Müller-Nurasyid
  98. Munich Heart Alliance, Munich, Germany.

    • Stefan Kääb
    •  & Annette Peters
  99. Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Bart Kanon
    •  & Ody C M Sibon
  100. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.

    • Kay-Tee Khaw
    •  & Robert N Luben
  101. Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

    • Joshua W Knowles
    • , Thomas Quertermous
    •  & Themistocles L Assimes
  102. Cardiology Department, Ealing Hospital National Health Service (NHS) Trust, London, UK.

    • Angrad S Kooner
    • , Jaban S Sehmi
    • , John C Chambers
    •  & Jaspal S Kooner
  103. Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Jan A Kors
    •  & Bruno H Ch Stricker
  104. Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, UK.

    • Meena Kumari
    • , Aroon Hingorani
    •  & Mika Kivimaki
  105. National Public Health Institute, Biomedicum Helsinki, Helsinki, Finland.

    • Päivi Laiho
  106. Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, USA.

    • Edward G Lakatta
    •  & Kirill V Tarasov
  107. Division Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.

    • Maarten Leusink
  108. Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina, USA.

    • Yongmei Liu
  109. Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA.

    • Kathryn L Lunetta
  110. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Kathryn L Lunetta
    • , Christopher J O'Donnell
    • , Shih-Jen Hwang
    •  & Christopher Newton-Cheh
  111. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

    • Marcello R P Markus
  112. Institut Universitaire de Médecine Sociale et Préventive (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.

    • Pedro Marques-Vidal
  113. School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • Wendy L McArdle
    •  & Susan M Ring
  114. Molecular Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • Grant W Montgomery
  115. Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.

    • Alanna C Morrison
  116. Chair of Genetic Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

    • Martina Müller-Nurasyid
  117. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Martina Müller-Nurasyid
  118. Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland.

    • Mari Nelis
  119. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Christopher J O'Donnell
  120. National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

    • Christopher J O'Donnell
  121. MRC Unit for Lifelong Health and Ageing, London, UK.

    • Ken K Ong
    • , Andrew Wong
    •  & Diana Kuh
  122. Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Anne B Newman
  123. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Annette Peters
  124. Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.

    • Ozren Polasek
  125. National Institute for Health and Welfare, Oulu, Finland.

    • Anneli Pouta
    •  & Marjo-Riitta Jarvelin
  126. Department of Neurology, General Central Hospital, Bolzano, Italy.

    • Peter P Pramstaller
  127. Department of Neurology, University of Lübeck, Lübeck, Germany.

    • Peter P Pramstaller
  128. Group Health Research Institute, Seattle, Washington, USA.

    • Bruce M Psaty
  129. Department of Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  130. Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Dabeeru C Rao
  131. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

  132. Harvard Biological and Biomedical Sciences Program, Harvard University, Boston, Massachusetts, USA.

  133. Health Science and Technology M.D. Program, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts, USA.

  134. Department of Pathophysiology, Faculty of Medicine, University of Split, Split, Croatia.

    • Diana Rudan
  135. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.

    • Serena Sanna
  136. National Heart and Lung Institute, Imperial College London, London, UK.

    • Jaban S Sehmi
    •  & Jaspal S Kooner
  137. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.

    • Andrew B Singleton
  138. Department of Twin Research and Genetic Epidemiology Unit, St. Thomas' Campus, King's College London, St. Thomas' Hospital, London, UK.

    • Nicole Soranzo
    • , Tim D Spector
    •  & Yalda Jamshidi
  139. Biology Department, Boston College, Chestnut Hill, Massachusetts, USA.

    • Chip Stewart
  140. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • André G Uitterlinden
    •  & Bruno H Ch Stricker
  141. Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • John B Whitfield
    •  & Nicholas G Martin
  142. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

    • Sarah H Wild
    • , James F Wilson
    •  & Igor Rudan
  143. Division of Biomedical Sciences, St. George's University of London, London, UK.

    • Yalda Jamshidi
  144. Department of Physiatrics, Lapland Central Hospital, Rovaniemi, Finland.

    • Paavo Zitting
  145. Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

    • Jolanda M A Boer
    •  & W M Monique Verschuren
  146. Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway.

    • Ulf Ekelund
  147. Genomic Medicine, Hammersmith Hospital, Imperial College London, London, UK.

    • Philippe Froguel
  148. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Erik Ingelsson
  149. Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.

    • Lars Lind
  150. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Ben A Oostra
  151. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Jerome I Rotter
  152. Institue of Cellular Medicine, Newcastle University, Newcastle, UK.

    • Mark Walker
  153. Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland.

    • David O Arnar
  154. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • David O Arnar
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  155. Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.

    • Stefania Bandinelli
  156. Channing Laboratory and Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Gary Curhan
  157. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Gary Curhan
  158. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.

    • Johan Eriksson
  159. Folkhälsan Research Centre, Helsinki, Finland.

    • Johan Eriksson
    •  & Bo Isomaa
  160. Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.

    • Johan Eriksson
  161. Hypertension and Related Diseases Centre–Azienda Ospedaliero Universitaria (AOU), University of Sassari, Sassari, Italy.

    • Nicola Glorioso
  162. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • David J Hunter
    •  & Peter Kraft
  163. Division of Research, Kaiser Permanente of Northern California, Oakland, California, USA.

    • Carlos Iribarren
  164. Department of Social Services and Health Care, Jakobstad, Finland.

    • Bo Isomaa
  165. Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  166. Institute of Health Sciences, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  167. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.

    • Antti Jula
  168. Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland.

    • Mika Kähönen
    •  & Terho Lehtimäki
  169. Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.

    • Lambertus A Kiemeney
  170. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

    • Lambertus A Kiemeney
  171. Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Melanie M van der Klauw
  172. Laboratory of Genetic and Environmental Epidemiology, Fondazione di Ricerca e Cura Giovanni Paolo II, Catholic University, Campobasso, Italy.

    • Licia Iacoviello
  173. Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.

    • Marja-Liisa L Lokki
  174. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Gerjan Navis
  175. Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.

    • Markku S Nieminen
    •  & Juha Sinisalo
  176. International Centre for Circulatory Health (ICCH), Imperial College London, London, UK.

    • Neil R Poulter
    •  & Peter S Sever
  177. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

    • Olli T Raitakari
  178. Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

    • Olli T Raitakari
  179. Kos Genetic, Milan, Italy.

    • Federica Rizzi
  180. Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin, Ireland.

    • Denis C Shields
  181. Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.

    • Denis C Shields
  182. School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin, Ireland.

    • Denis C Shields
  183. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, USA.

    • Alan R Shuldiner
  184. Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.

    • Alice V Stanton
  185. Diabetes Unit, National Institute for Health and Welfare, Helsinki, Finland.

    • Jaako Tuomilehto
  186. Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.

    • Jaako Tuomilehto
  187. Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (Red RECAVA), Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.

    • Jaako Tuomilehto
  188. King Abdulaziz University, Jeddah, Saudi Arabia.

    • Jaako Tuomilehto
  189. Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.

    • Jorma Viikari
  190. Department of Internal Medicine, University Hospital of Lausanne, Lausanne, Switzerland.

    • Peter Vollenweider
    •  & Gérard Waeber
  191. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Elisabeth Widen
  192. Department of Biomedical Science, Hallym University, Chuncheon, Korea.

    • Yoon Shin Cho
  193. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.

    • Peter M Visscher
  194. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

    • Cristen Willer
  195. Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Lude Franke
  196. Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.

    • Jeanette Erdmann
  197. DZHK, partner site Hamburg/Kiel/Lübeck, Lübeck, Germany.

    • Jeanette Erdmann
  198. Department of Health Sciences, University of Leicester, Leicester, UK.

    • John R Thompson
  199. Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Munich, Germany.

    • Arne Pfeufer
  200. Institute of Human Genetics, Klinikum Rechts der Isar der Technischen Universitat München, Munich, Germany.

    • Arne Pfeufer
  201. Department of Medicine, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.

    • Nona Sotoodehnia
  202. Center for Human Genetic Research, Cardiovacular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Christopher Newton-Cheh
  203. Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Patrick T Ellinor
  204. Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.

    • Patrick T Ellinor
  205. Inspectorate of Health Care, The Hague, The Netherlands.

    • Bruno H Ch Stricker
  206. Service of Medical Genetics, CHUV University Hospital, Lausanne, Switzerland.

    • Jacques S Beckmann
  207. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • David J Milan
  208. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
  209. NIHR Leicester Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
  210. The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Ruth J F Loos
  211. The Charles Bronfman Institute of Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Ruth J F Loos
  212. The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Ruth J F Loos

Consortia

  1. Global BPgen Consortium

    A full list of members appears in the Supplementary Note.

  2. CARDIoGRAM Consortium

    A full list of members appears in the Supplementary Note.

  3. PR GWAS Consortium

    A full list of members appears in the Supplementary Note.

  4. QRS GWAS Consortium

    A full list of members appears in the Supplementary Note.

  5. QT-IGC Consortium

    A full list of members appears in the Supplementary Note.

  6. CHARGE-AF Consortium

    A full list of members appears in the Supplementary Note.

Authors

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Contributions

Steering committee (oversaw the project): M. den Hoed (lead) and R.J.F.L. (chair). Writing group (drafted the manuscript): M.E., M. den Hoed (chair), R.J.F.L. and N.J.S. Editing group (edited the manuscript): B.J.J.M.B., P.T.E., T.E., D.M.E., E.J.C.d.G., M. den Hoed (chair), E.I., D.J.M., R.J.F.L., A.L., D.J.M., I.M.N., A.V. Segrè, O.C.M.S., H.S., J.R.T. and N.J.T. Meta-analysis working group (performed stage 1 and stage 2 meta-analyses): T.E. and M. den Hoed (chair). Data preparation working group (prepared data from contributing cohorts for meta-analyses): M.E., T.E., M. den Hoed (lead) and R.J.F.L. (chair). Conditional analyses: M. den Hoed, R.J.F.L., P.M.V. (chair) and J.Y. (lead). Genetic predisposition score analyses: D.M.E., M. den Hoed (chair) and I.M.N. Association analyses with related traits: C.M.A., P.I.W.d.B., CARDIoGRAM Consortium, CHARGE-AF Consortium, Y.S.C., M.C., D.D., P.T.E., J. Erdmann, Global BPgen Consortium, M.J.G., M. den Hoed (chair), H.H., A.I., T.J., S. Kääb, Y.J.K., K.L.L., P.B.M., C.N.-C., A. Pfeufer, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, N.J.S., S. Sharp, N. Sotoodehnia and J.R.T. Copy number variant analyses: R.E.H. (lead), M. den Hoed (chair), S.A.M. and C. Stewart. Gene eQTL analyses: L. Franke (chair), M. den Hoed and H.-J.W. (lead). Proteomics experiments and genetic enrichment analyses: M. den Hoed, R.J.F.L., A.L. (lead), E.J.R. and J.V.O. (chair). SNIPPER analyses for selection of positional candidate genes: M. den Hoed (chair), R.J.F.L. and C. Willer (lead). Pathway analyses: M. den Hoed (chair), R.J.F.L. and A.V. Segrè (lead). D. melanogaster experiments: B.J.J.M.B. (lead), M. den Hoed, F.H.-B., B.K., R.J.F.L., O.C.M.S. (chair) and H.S. D. rerio experiments: M. den Hoed, R.J.F.L., S.N.L., D.J.M. (chair), D.S.P. (lead) and J.T.S.

Project design, management and coordination of contributing cohorts

Stage 1–GWAS: (ADVANCE) T.L.A., C.I. and T.Q.; (ALSPAC) G.D.S.; (ASCOT cases) N.R.P., P.S.S., D.C.S. and A.V. Stanton; (ATBC) D. Albanes and J. Virtamo; (B58C) W.L.M.C. and D.P.S.; (BLSA) S. Bandinelli and L. Ferrucci; (BRIGHT) M.C., T.J., P.B.M. and N.J.S.; (CoLaus) J.S.B., P.V. and G. Waeber; (COROGENE) M.-L.L.L., M.S.N., M.P. and J.S.; (deCODE) D.O.A., K.S. and U.T.; (DGI) L.G. and B.I.; (EGCUT) A.M.; (EPIC-Norfolk) N.J.W.; (Fenland) U.E., N.G.F., R.J.F.L. and N.J.W.; (Fingesture) H.V.H., J.D.R. and J.-C.T.; (Finrisk07) M.P. and V.S.; (FUSION) M. Boehnke and J.T.; (GOOD) C.O.; (HAPI) B.D.M. and A.R.S.; (HBCS) J. Eriksson, M.P. and E.W.; (Health 2000) A.J. and M.P.; (Health ABC) W.-C.H.; (HERITAGE) C. Bouchard, T.R. and D.C.R.; (HPFS) G.C., F.B.H., D.J.H., P.K., L.Q. and E.B.R.; (Hypergenes) D.C., N.G., L.I. and F.R.; (InCHIANTI) S. Bandinelli and L. Ferrucci; (Korcula) I.R.; (LifeLines) R.A.d.B., M.M.v.d.K., H.S. and R.P.S.; (Lolipop) J.C.C. and J.S.K.; (NBS) J.d.G. and L.A.K.; (NFBC1966) M.-R.J.; (NHS) G.C., F.B.H., D.J.H., P.K., L.Q. and E.B.R.; (NSPHS) U.G.; (PREVEND) W.H.v.G., G.N. and D.J.v.V.; (SPLIT) I.R.; and (YFS) M. Kähönen, T.L., M.P., O.T.R. and J. Viikari. Stage 2–in silico replication studies: (AGES, RRgen) V.G. and T.B.H.; (ACTS) N.G.M.; (ALSPAC) G.D.S.; (ARIC, RRgen) A.A.; (CHS, RRgen) B.M.P.; (DESIR) N.B.-N.; (EGCUT) A.M.; (Ely) N.J.W.; (EPIC-NL) J.M.A.B., Y.T.v.d.S. and W.M.M.V.; (EPIC-Norfolk) N.J.W.; (ERF) C.M.v.D. and B.A.O.; (FamHS) I.B.B.; (Fenland) U.E., N.G.F., R.J.F.L. and N.J.W.; (FHS, RRgen) C.J.O.; (Finrisk07) M.P. and V.S.; (KORA, RRgen) A. Peters and S. Kääb; (LifeLines2) R.A.d.B., M.M.v.d.K., H.S. and R.P.S.; (MESA) R.A.K. and J.I.R.; (MICROS, RRgen) P.P.P.; (NSHD) D.K.; (NTR) D.I.B. and E.J.C.d.G.; (ORCADES, RRgen) J.F.W.; (RISC) M.W.; (PIVUS) E.I. and L.L.; (RS1-3) A. Hofman, B.H.Ch.S. and J.C.M.W.; (SardiNIA, RRgen) E.G.L. and K.V.T.; (SHIP, RRgen) M.D. and S.B.F.; (Stanford IST) T.Q.; (STR) E.I. and N.L.P.; (Twins UK, RRgen) Y.J. and T.D.S.; (ULSAM) E.I.; and (Whitehall II) A. Hingorani and M. Kivimaki.

Genotyping of contributing cohorts

Stage 1–GWAS: (ADVANCE) D. Absher; (ALSPAC) S.M.R. and W.L.M.; (ATBC) S.J.C.; (BLSA) L. Ferrucci and A.B.S.; (BRIGHT) M.C. and P.B.M.; (COROGENE) P.S.; (EGCUT) T.E., L.M. and M.N.; (EPIC-Norfolk) R.J.F.L. and J.H.Z.; (Fenland) J.L.; (Fingesture) P.G. and J.D.R.; (Finrisk07) P.S.; (FUSION) P.S.C.; (GOOD) M. Lorentzon and C.O.; (HBCS) P.S.; (Health2000) P.L. and P.S.; (Health ABC) Y.L.; (HERITAGE) C. Bouchard and T.R.; (HPFS) M.C.C. and M.K.J.; (Hypergenes) C. Barlassina and P.B.; (InCHIANTI) L. Ferrucci and A.B.S.; (Korcula) C.H.; (LifeLines) L. Franke; (Lolipop) J.C.C. and J.S.K.; (NBS) L.A.K.; (NFBC1966) P.E., A.-L.H., M.-R.J. and P.Z.; (NHS) M.C.C. and M.K.J.; (NSPHS) Å.J.; (PREVEND) P.v.d.H.; (SPLIT) C.H. and V.V.; and (YFS) M. Kähönen, T.L., M.P., O.T.R., P.S. and J. Viikari. Stage 2–in silico replication studies: (ACTS) N.G.M., S.E.M. and G.W.M.; (ALSPAC) S.M.R. and W.L.M.; (ARIC, RRgen) D.E.A.; (DESIR) N.B.-N.; (EGCUT) T.E., L.M. and M.N.; (EPIC-NL) N.C.O.-M. and C. Wijmenga; (ERF) C.M.v.D., A.I. and B.A.O.; (Ely) R.J.F.L. and J.L.; (EPIC-Norfolk) R.J.F.L. and J.H.Z.; (FamHS) I.B.B. and M.F.F.; (Fenland) J.L.; (Finrisk07) P.S.; (LifeLines2) L. Franke; (MESA) J.I.R.; (NSHD) D.K., K.K.O. and A.W.; (NTR) D.I.B. and J.-J.H.; (PIVUS) E.I. and L.L.; (RS1-3) A.G.U.; (Stanford IST) T.L.A. and J.W.K.; (STR) E.I. and N.L.P.; (ULSAM) E.I.; and (Whitehall II) M. Kumari and C. Langenberg.

Phenotyping of contributing cohorts

Stage 1–GWAS: (ADVANCE) C.I.; (ASCOT cases) N.R.P., P.S.S. and A.V. Stanton; (ATBC) D. Albanes and J. Virtamo; (B58C) D.P.S.; (BLSA) S. Bandinelli and L. Ferrucci; (BRIGHT) M.C. and N.J.S.; (CoLaus) P.M.-V.; (COROGENE) M.P.; (deCODE) D.O.A. and H.H.; (DGI) B.I.; (EGCUT) K.F. and A.M.; (EPIC-Norfolk) K.-T.K.; (Fingesture) H.V.H. and J.J.; (Finrisk07) M.P.; (FUSION) H.M.S.; (GOOD) M. Lorentzon, C.O. and L.V.; (HBCS) J. Eriksson, M.P. and E.W.; (Health2000) A.J. and M.P.; (Health ABC) A.B.N.; (HERITAGE) C. Bouchard; (Hypergenes) D.C., N.G., L.I. and F.R.; (InCHIANTI) S. Bandinelli and L. Ferrucci; (Korcula) O.P.; (LifeLines) R.A.d.B., M.M.v.d.K. and R.P.S.; (Lolipop) J.C.C., A.S.K., J.S.K., K.A.M. and J.S.S.; (NBS) S.H.; (NFBC1966) A.-L.H., M.-R.J., A. Pouta and P.Z.; (PREVEND) R.A.d.B., W.H.v.G. and P.v.d.H.; (SPLIT) D.R.; and (YFS) M. Kähönen, T.L., M.P., O.T.R., P.S. and J. Viikari. Stage 2–in silico replication studies: (AGES, RRgen) V.G.; (ACTS) N.G.M. and J.B.W.; (CHS, RRgen) N. Sotoodehnia; (DESIR) B.B. and P.F.; (EGCUT) K.F. and A.M.; (Ely) S. Brage and U.E.; (EPIC-NL) J.M.A.B., Y.T.v.d.S. and W.M.M.V.; (EPIC-Norfolk) K.-T.K.; (ERF) C.M.v.D., A.I., J.A.K. and B.A.O.; (FamHS) I.B.B. and M.F.F.; (FHA, RRgen) C.N.-C.; (Finrisk07) M.P.; (LifeLines2) R.A.d.B., M.M.v.d.K. and R.P.S.; (MESA) S.R.H. and R.A.K.; (MICROS, RRgen) A.A.H.; (NSHD) D.K.; (NTR) D.I.B., E.J.C.d.G. and G. Willemsen; (ORCADES, RRgen) S.H.W.; (PIVUS) E.I. and L.L.; (RISC) M.W.; (RS1-3) B.H.Ch.S. and A.G.U.; (SHIP, RRgen) M.D. and M.R.P.M.; (Stanford IST) T.L.A. and J.W.K.; (STR) E.I. and N.L.P.; (ULSAM) E.I.; and (Whitehall II) M. Kumari.

Analyses of contributing cohorts

Stage 1–GWAS: (ADVANCE) T.L.A. and L.W.; (ALSPAC) D.M.E., J.P.K., B.S.P. and N.J.T.; (ASCOT cases) T.J.; (ATBC) W.W.; (B58C) D.H. and D.P.S.; (BLSA) T.T.; (BRIGHT) T.J. and S.P.; (CoLaus) M. Bochud and Z.K.; (COROGENE) P.S.; (deCODE) D.G. and H.H.; (DGI) P.A., C. Ladenvall and R.A.S.; (EGCUT) T.E. and E.M.; (EPIC-Norfolk) M. den Hoed, R.N.L. and J.H.Z.; (Fenland) M. den Hoed and J.L.; (Fingesture) G.B. and P.G.; (Finrisk07) A.S.H., K.K. and P.S.; (FUSION) A.U.J.; (GOOD) M. Lorentzon, C.O. and L.V.; (HAPI) M.E.M. and J.R.O.; (HBCS,) P.S.; (Health2000) P.S.; (Health ABC) W.-C.H. and O.T.N.; (HERITAGE) C. Bouchard, T.R. and D.C.R.; (HPFS) M.C.C. (InCHIANTI) T.T.; (Korcula) C.H.; (LifeLines) I.M.N. and H.S.; (Lolipop) J.C.C., J.S.K., J.S.S. and W.Z.; (NBS) M. den Heijer; (NFBC1966) P.F.O.; (NHS) M.C.C.; (Hypergenes) D.C.; (NSPHS) W.I.; (PREVEND) P.v.d.H. and I.M.L.; (SPLIT) C.H. and V.V.; and (YFS) P.S. Stage 2–in silico replication studies: (AGES, RRgen) A.V. Smith; (ACTS) P.A.L.; (ALSPAC) D.M.E., J.P.K., B.S.P. and N.J.T.; (ARIC, RRgen) A.C.M.; (CHS, RRgen) J.C.B. and N. Sotoodehnia; (DESIR) C.D., N.B.-N. and L.Y.; (EGCUT) T.E. and E.M.; (Ely) M. den Hoed and J.L.; (EPIC-NL) M. Leusink and N.C.O.-M.; (EPIC-Norfolk) M. den Hoed, R.N.L. and J.H.Z.; (ERF) A.I.; (FamHS) M.F.F. and S. Ketkar; (Fenland) M. den Hoed and J.L.; (FHS, RRgen) C.N.-C. and S.-J.H.; (Finrisk07) A.S.H. and K.K., P.S.; (KORA, RRgen) M.M.-N.; (LifeLines2) I.M.N. and H.S.; (MESA) K.F.K. and Q.W.; (MICROS, RRgen) C.F.; (NSHD) M. den Hoed, J.L. and A.W.; (NTR) H.H.M.D. and J.-J.H.; (ORCADES, RRgen) P.N.; (PIVUS) E.I. and C. Song; (RISC) M.N.W. and W.X.; (RRgen) P.I.W.d.B.; (RS1-3) P.I.W.d.B. and M.E.; (SardiNIA, RRgen) S. Sanna; (Stanford IST) W.X.; (STR) E.I. and C. Song; (Twins UK, RRgen) N. Soranzo; (ULSAM) E.I. and C. Song; and (Whitehall II) M. den Hoed and J.L.

The corresponding author (R.J.F.L.) had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Competing interests

N.R.P. and A.V. Stanton have received financial support from several pharmaceutical companies that manufacture either blood pressure–lowering or lipid-lowering agents or both for consultancy fees, research projects and staff and for arranging and speaking at educational meetings. They do not hold stock or shares in any such companies. The authors that are affiliated with deCODE Genetics (H.H., D.G., U.T. and K.S.) are all employees of deCODE, a biotechnology company that provides genetic testing services, and some own stock or stock options in the company. F.H.-B. is an employee of Nyken, which holds intellectual property interests in heat shock protein expression as a treatment for atrial fibrillation. F.H.-B. does not hold stock or shares in Nyken. None of the other authors disclose competing financial interests.

Corresponding author

Correspondence to Ruth J F Loos.

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https://doi.org/10.1038/ng.2610

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