Article | Published:

A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease

Nature Genetics volume 47, pages 11211130 (2015) | Download Citation

This article has been updated

Abstract

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

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Change history

  • 14 September 2015

    In the version of this article initially published online, there was a typographical error in the third sentence of the abstract. The corrected sentence should read: "In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls." The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We sincerely thank the participants and the medical, nursing, technical and administrative staff in each of the studies who have contributed to this project. We are grateful for support from our funders; more detailed acknowledgments are included in the Supplementary Note.

Author information

Author notes

    • Majid Nikpay
    • , Anuj Goel
    • , Hong-Hee Won
    • , Leanne M Hall
    • , Christina Willenborg
    • , Stavroula Kanoni
    •  & Danish Saleheen

    These authors contributed equally to this work.

    • Hugh Watkins
    • , Sekar Kathiresan
    • , Ruth McPherson
    • , Panos Deloukas
    • , Heribert Schunkert
    • , Nilesh J Samani
    •  & Martin Farrall

    These authors jointly supervised this work.

Affiliations

  1. Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

    • Majid Nikpay
    • , Alexandre F Stewart
    •  & Ruth McPherson
  2. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

    • Anuj Goel
    • , Theodosios Kyriakou
    • , Christopher Grace
    • , Shapour Jalilzadeh
    • , Hugh Watkins
    •  & Martin Farrall
  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Anuj Goel
    • , Theodosios Kyriakou
    • , Christopher Grace
    • , Natalie R van Zuydam
    • , Shapour Jalilzadeh
    • , Cecilia M Lindgren
    • , Andrew P Morris
    • , Erik Ingelsson
    • , Hugh Watkins
    •  & Martin Farrall
  4. Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA.

    • Hong-Hee Won
    • , Andrew Bjonnes
    • , Richa Saxena
    • , Cecilia M Lindgren
    • , Tõnu Esko
    •  & Sekar Kathiresan
  5. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Hong-Hee Won
    •  & Sekar Kathiresan
  6. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Hong-Hee Won
    • , Andrew Bjonnes
    • , Richa Saxena
    •  & Sekar Kathiresan
  7. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Hong-Hee Won
    •  & Sekar Kathiresan
  8. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

    • Leanne M Hall
    • , Christopher P Nelson
    • , Thomas R Webb
    •  & Nilesh J Samani
  9. Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany.

    • Christina Willenborg
    •  & Jeanette Erdmann
  10. DZHK (German Research Center for Cardiovascular Research), partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.

    • Christina Willenborg
    • , Inke R König
    •  & Jeanette Erdmann
  11. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Stavroula Kanoni
    • , Kathleen E Stirrups
    •  & Panos Deloukas
  12. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Danish Saleheen
    •  & Wei Zhao
  13. Center for Non-Communicable Diseases, Karachi, Pakistan.

    • Danish Saleheen
    • , Philippe Frossard
    • , Asif Rasheed
    •  & Maria Samuel
  14. National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.

    • Christopher P Nelson
    • , Thomas R Webb
    • , Alison H Goodall
    •  & Nilesh J Samani
  15. Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

    • Jemma C Hopewell
    • , King Wai Lau
    • , Rory Collins
    •  & Robert Clarke
  16. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.

    • Lingyao Zeng
    • , Thorsten Kessler
    • , Christian Hengstenberg
    •  & Heribert Schunkert
  17. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.

    • Lingyao Zeng
    • , Christian Gieger
    • , Thomas Meitinger
    • , Annette Peters
    • , Christian Hengstenberg
    •  & Heribert Schunkert
  18. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.

    • Abbas Dehghan
    • , Andre Uitterlinden
    • , Paul S de Vries
    • , Oscar H Franco
    •  & Albert Hofman
  19. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Maris Alver
    • , Evelin Mihailov
    • , Natalia Pervjakova
    • , Tõnu Esko
    • , Andres Metspalu
    •  & Markus Perola
  20. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Maris Alver
    •  & Andres Metspalu
  21. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

    • Sebastian M Armasu
    •  & Mariza de Andrade
  22. Department of Health, National Institute for Health and Welfare, Helsinki, Finland.

    • Kirsi Auro
    • , Natalia Pervjakova
    •  & Markus Perola
  23. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Kirsi Auro
    • , Natalia Pervjakova
    • , Emmi Tikkanen
    • , Markus Perola
    •  & Samuli Ripatti
  24. Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland.

    • Kirsi Auro
    • , Natalia Pervjakova
    •  & Markus Perola
  25. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Daniel I Chasman
    • , Lynda M Rose
    • , Julie E Buring
    •  & Paul M Ridker
  26. Harvard Medical School, Boston, Massachusetts, USA.

    • Daniel I Chasman
    •  & Paul M Ridker
  27. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Shufeng Chen
    • , Xiangfeng Lu
    • , Xueli Yang
    • , Laiyuan Wang
    •  & Dongfeng Gu
  28. Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.

    • Ian Ford
  29. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Nora Franceschini
  30. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Christian Gieger
    •  & Annette Peters
  31. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Christian Gieger
  32. Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

    • Stefan Gustafsson
    •  & Erik Ingelsson
  33. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

    • Stefan Gustafsson
    •  & Erik Ingelsson
  34. Wellcome Trust Sanger Institute, Hinxton, UK.

    • Jie Huang
    • , John Danesh
    •  & Samuli Ripatti
  35. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Shih-Jen Hwang
    • , L Adrienne Cupples
    •  & Christopher J O'Donnell
  36. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Shih-Jen Hwang
    •  & L Adrienne Cupples
  37. Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Korea.

    • Yun Kyoung Kim
    • , Bok-Ghee Han
    •  & Bong-Jo Kim
  38. Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.

    • Marcus E Kleber
    •  & Winfried März
  39. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Yingchang Lu
    • , Omri Gottesman
    • , Erwin P Bottinger
    •  & Ruth J F Loos
  40. Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Yingchang Lu
    •  & Ruth J F Loos
  41. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.

    • Leo-Pekka Lyytikäinen
    • , Pekka J Karhunen
    •  & Terho Lehtimäki
  42. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  43. Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Alanna C Morrison
    •  & Eric Boerwinkle
  44. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Liming Qu
  45. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, California, USA.

    • Elias Salfati
    • , Erik Ingelsson
    • , Thomas Quertermous
    •  & Themistocles L Assimes
  46. Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Richa Saxena
  47. Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, Germany.

    • Markus Scholz
  48. LIFE Research Center of Civilization Diseases, Leipzig, Germany.

    • Markus Scholz
    • , Frank Beutner
    •  & Joachim Thiery
  49. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    •  & Vilmundur Gudnason
  50. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    •  & Vilmundur Gudnason
  51. Department of Public Health, University of Helsinki, Helsinki, Finland.

    • Emmi Tikkanen
    •  & Samuli Ripatti
  52. Department of Epidemiology and Biostatistics, Imperial College London, London, UK.

    • Weihua Zhang
    •  & John C Chambers
  53. Department of Cardiology, Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.

    • Weihua Zhang
    • , John C Chambers
    •  & Jaspal S Kooner
  54. Medical Research Institute, University of Dundee, Dundee, UK.

    • Natalie R van Zuydam
    •  & Colin N Palmer
  55. Population Health Research Institute, Hamilton Health Sciences, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

    • Sonia S Anand
  56. Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.

    • Lars Bertram
  57. Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK.

    • Lars Bertram
  58. Heart Center Leipzig, Cardiology, University of Leipzig, Leipzig, Germany.

    • Frank Beutner
  59. Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.

    • George Dedoussis
  60. INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France.

    • Dominique Gauguier
  61. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Alison H Goodall
  62. School of Medicine, Lebanese American University, Beirut, Lebanon.

    • Marc Haber
    •  & Pierre A Zalloua
  63. Hypertension Division, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Jianfeng Huang
  64. Klinikum Rechts der Isar, Munich, Germany.

    • Thorsten Kessler
  65. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.

    • Inke R König
  66. Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.

    • Lars Lannfelt
  67. Institut für Epidemiologie, Christian Albrechts Universität zu Kiel, Kiel, Germany.

    • Wolfgang Lieb
  68. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.

    • Lars Lind
  69. Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.

    • Marja-Liisa Lokki
  70. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Patrik K Magnusson
    •  & Nancy L Pedersen
  71. Punjab Institute of Cardiology, Lahore, Pakistan.

    • Nadeem H Mallick
  72. All India Institute of Medical Sciences, New Delhi, India.

    • Narinder Mehra
  73. Institut für Humangenetik, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Thomas Meitinger
  74. Institute of Human Genetics, Technische Universität München, Munich, Germany.

    • Thomas Meitinger
  75. Red Crescent Institute of Cardiology, Hyderabad, Pakistan.

    • Fazal-ur-Rehman Memon
    •  & Asif Rasheed
  76. Department of Biostatistics, University of Liverpool, Liverpool, UK.

    • Andrew P Morris
  77. Department of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.

    • Markku S Nieminen
    •  & Juha Sinisalo
  78. Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.

    • Loukianos S Rallidis
  79. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

    • Svati H Shah
    •  & Christopher B Granger
  80. Department of Haematology, University of Cambridge, Cambridge, UK.

    • Kathleen E Stirrups
  81. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.

    • Stella Trompet
    •  & J Wouter Jukema
  82. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.

    • Stella Trompet
  83. National Human Genome Center at Beijing, Beijing, China.

    • Laiyuan Wang
  84. National Institute of Cardiovascular Diseases, Karachi, Pakistan.

    • Khan S Zaman
  85. Division of Cardiology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy.

    • Diego Ardissino
  86. Associazione per lo Studio della Trombosi in Cardiologia, Pavia, Italy.

    • Diego Ardissino
  87. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

    • Eric Boerwinkle
  88. Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Ingrid B Borecki
    •  & Mary F Feitosa
  89. Imperial College Healthcare NHS Trust, London, UK.

    • John C Chambers
    •  & Jaspal S Kooner
  90. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • John Danesh
  91. Berlin Aging Study II; Research Group on Geriatrics, Charité Universitätsmedizin Berlin, Berlin, Germany.

    • Ilja Demuth
  92. Institute of Medical and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.

    • Ilja Demuth
  93. Grupo de Epidemiología y Genética Cardiovascular, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.

    • Roberto Elosua
  94. MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC, USA.

    • Stephen E Epstein
  95. Division of Endocrinology and Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.

    • Tõnu Esko
  96. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Tõnu Esko
  97. Department of Cardiovascular Research, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

    • Maria Grazia Franzosi
  98. Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.

    • Alistair S Hall
  99. Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

    • Anders Hamsten
  100. Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.

    • Tamara B Harris
  101. Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.

    • Stanley L Hazen
  102. Kaiser Permanente Division of Research, Oakland, California, USA.

    • Carlos Iribarren
  103. Durrer Center for Cardiogenetic Research, Amsterdam, the Netherlands.

    • J Wouter Jukema
  104. Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.

    • J Wouter Jukema
  105. Department of Forensic Medicine, University of Tampere School of Medicine, Tampere, Finland.

    • Pekka J Karhunen
  106. Cardiovascular Science, National Heart and Lung Institute, Imperial College London, London, UK.

    • Jaspal S Kooner
  107. Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

    • Iftikhar J Kullo
  108. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Ruth J F Loos
  109. Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Lund University, University Hospital Malmö, Malmö, Sweden.

    • Olle Melander
  110. Synlab Academy, Synlab Services, Mannheim, Germany.

    • Winfried März
  111. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

    • Winfried März
  112. Stanford Cardiovascular Institute, Stanford University, Stanford, California, USA.

    • Thomas Quertermous
    •  & Themistocles L Assimes
  113. Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Daniel J Rader
  114. Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Daniel J Rader
    •  & Muredach P Reilly
  115. University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

    • Robert Roberts
  116. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Veikko Salomaa
  117. Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

    • Dharambir K Sanghera
  118. Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

    • Dharambir K Sanghera
  119. Oklahoma Center for Neuroscience, Oklahoma City, Oklahoma, USA.

    • Dharambir K Sanghera
  120. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Stephen M Schwartz
  121. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Stephen M Schwartz
  122. Department of Prosthetic Dentistry, Center for Dental and Oral Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

    • Udo Seedorf
  123. Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, UK.

    • David J Stott
  124. Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Medical Faculty, Leipzig, Germany.

    • Joachim Thiery
  125. Harvard School of Public Health, Boston, Massachusetts, USA.

    • Pierre A Zalloua
  126. National Heart, Lung, and Blood Institute Division of Intramural Research, Bethesda, Maryland, USA.

    • Christopher J O'Donnell
  127. Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Christopher J O'Donnell
  128. Department of Health Sciences, University of Leicester, Leicester, UK.

    • John R Thompson
  129. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.

    • Panos Deloukas

Consortia

  1. the CARDIoGRAMplusC4D Consortium

Authors

    Contributions

    Cohort oversight: D.A., E.B., I.B.B., E.P.B., J.E.B., J.C.C., R. Collins, L.A.C., J.D., I.D., R.E., S.E.E., T.E., M.F.F., O.H.F., M.G.F., C.B.G., D. Gu, V.G., A.S.H., A. Hamsten, T.B.H., S.L.H., C.H., A. Hofman, E.I., C.I., J.W.J., P.J.K., B.-J.K., J.S.K., I.J.K., T.L., R.J.F.L., O.M., A.M., W.M., C.N.P., M.P., T.Q., D.J.R., P.M.R., S.R., R.R., V.S., D.K.S., S.M.S., U.S., A.F.S., D.J.S., J.T., P.A.Z., C.J.O'D., M.P.R., T.L.A., J.R.T., J.E., H.W., S. Kathiresan, R.M., P.D., H.S., N.J.S. and M.F. Cohort genotyping: H.-H.W., S. Kanoni, D.S., J.C.H., Jie Huang, M.E.K., Y.L., L.-P.L., A.U., S.S.A., L.B., G.D., D. Gauguier, A.H.G., M.H., B.-G.H., S.J., L. Lind, C.M.L., M.-L.L., P.K.M., A.P.M., M.S.N., N.L.P., J.S., K.E.S., S.T., L.W., I.B.B., J.C.C., R. Collins, M.F.F., A. Hofman, E.I., J.S.K., T.L., R.R., D.K.S., A.F.S., R. Clarke, P.D. and N.J.S. Cohort phenotyping: D.S., J.C.H., A.D., M.A., K.A., Y.K.K., E.M., L.M.R., S.S.A., F.B., G.D., P.F., A.H.G., O.G., Jianfeng Huang, T. Kessler, I.R.K., L. Lannfelt, W.L., L. Lind, C.M.L., P.K.M., N.H.M., N.M., T.M., F.-ur-R.M., A.P.M., N.L.P., A.P., L.S.R., A.R., M. Samuel, S.H.S., K.S.Z., D.A., J.E.B., J.C.C., R. Collins, R.E., C.B.G., V.G., A.S.H., A. Hamsten, S.L.H., E.I., J.W.J., P.J.K., J.S.K., I.J.K., O.M., A.M., M.P., R.R., D.K.S., A.F.S., D.J.S., P.A.Z., M.P.R., R. Clarke, S. Kathiresan, H.S. and N.J.S. Cohort data analyst: M.N., A.G., H.-H.W., L.M.H., C.W., S. Kanoni, D.S., T. Kyriakou, C.P.N., J.C.H., T.R.W., L.Z., A.D., M.A., S.M.A., K.A., A.B., D.I.C., S.C., I.F., N.F., C. Gieger, C. Grace, S.G., Jie Huang, S.-J.H., Y.K.K., M.E.K., K.W.L., X.L., Y.L., L.-P.L., E.M., A.C.M., N.P., L.Q., L.M.R., E.S., R.S., M. Scholz, A.V.S., E.T., A.U., X.Y., W. Zhang, W. Zhao, M.d.A., P.S.d.V., N.R.v.Z., M.F.F., J.R.T. and M.F. Meta-analysis: M.N., A.G., H.-H.W., L.M.H., C.P.N., J.R.T. and M.F. Variant annotation: M.N., A.G., H.-H.W., T. Kyriakou, J.C.H. and T.R.W. Manuscript drafting: M.N., A.G., H.-H.W., L.M.H., T. Kyriakou, J.C.H., H.W., S. Kathiresan, R.M., H.S., N.J.S. and M.F. Project steering committee: M.N., A.G., H.-H.W., L.M.H., S. Kanoni., J.C.H., D.I.C., M.E.K., N.R.v.Z., C.N.P., R.R., C.J.O'D., M.P.R., T.L.A., J.R.T., J.E., R. Clarke, H.W., S. Kathiresan, R.M., P.D., H.S., N.J.S. and M.F. (secretariat: J.C.H. and R. Clarke). CARDIoGRAMplusC4D executive committee: J.D., D. Gu, A. Hamsten, J.S.K., R.R., H.W., S. Kathiresan, P.D., H.S. and N.J.S.

    Competing interests

    The author declare no competing financial interests.

    Corresponding authors

    Correspondence to Hugh Watkins or Sekar Kathiresan or Ruth McPherson or Martin Farrall.

    Integrated supplementary information

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      Supplementary Tables 1–15

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    DOI

    https://doi.org/10.1038/ng.3396

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