Article | Published:

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Nature Genetics volume 48, pages 11711184 (2016) | Download Citation

Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

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Acknowledgements

We thank all the participants of this study for their contributions. Detailed acknowledgment of funding sources by study is provided in the Supplementary Note.

Author information

Author notes

    • Georg B Ehret
    •  & Teresa Ferreira

    These authors contributed equally to this work.

    • Andrew P Morris
    • , Christopher Newton-Cheh
    •  & Patricia B Munroe

    These authors jointly directed this work.

Affiliations

  1. Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Georg B Ehret
    • , Vasyl Pihur
    • , Dan E Arking
    • , Maria X Sosa
    •  & Aravinda Chakravarti
  2. Cardiology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.

    • Georg B Ehret
    • , Li Lin
    •  & François Mach
  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Teresa Ferreira
    • , Martin Farrall
    • , Anuj Goel
    • , Mark I McCarthy
    • , N William Rayner
    • , Hugh Watkins
    •  & Andrew P Morris
  4. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Daniel I Chasman
    • , Franco Giulianini
    • , Lynda M Rose
    •  & Paul M Ridker
  5. Harvard Medical School, Boston, Massachusetts, USA.

    • Daniel I Chasman
    •  & Paul M Ridker
  6. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

    • Anne U Jackson
    • , Michael Boehnke
    • , Hyun Min Kang
    • , Xueling Sim
    •  & Heather M Stringham
  7. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Anne U Jackson
    • , Michael Boehnke
    • , Hyun Min Kang
    • , Xueling Sim
    •  & Heather M Stringham
  8. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.

    • Ellen M Schmidt
    •  & Cristen J Willer
  9. Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, UK.

    • Toby Johnson
    • , Kate Witkowska
    • , Helen Warren
    • , Claudia P Cabrera
    • , Mark J Caulfield
    •  & Patricia B Munroe
  10. GlaxoSmithKline, Stevenage, UK.

    • Toby Johnson
  11. deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.

    • Gudmar Thorleifsson
    • , Gyda Bjornsdottir
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  12. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.

    • Jian'an Luan
    • , Ken K Ong
    • , Nicholas J Wareham
    • , Jing Hua Zhao
    • , Claudia Langenberg
    •  & Ruth J F Loos
  13. Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.

    • Louise A Donnelly
    • , Alex S F Doney
    • , Andrew D Morris
    •  & Colin N A Palmer
  14. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Stavroula Kanoni
    • , Lazaros Lataniotis
    • , Michael R Barnes
    • , Eirini Marouli
    • , Kathleen E Stirrups
    • , Tsun-Po Yang
    •  & Panos Deloukas
  15. Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.

    • Ann-Kristin Petersen
    •  & Martina Müller-Nurasyid
  16. Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Rona J Strawbridge
    • , Lasse Folkersen
    • , Per Eriksson
    • , Karl Gertow
    •  & Anders Hamsten
  17. Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.

    • Rona J Strawbridge
    • , Karl Gertow
    •  & Anders Hamsten
  18. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

    • Dmitry Shungin
    • , Göran Hallmans
    • , Frida Renström
    •  & Paul W Franks
  19. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund Universityö, Malmö, Sweden.

    • Dmitry Shungin
    • , Frida Renström
    •  & Paul W Franks
  20. Department of Odontology, Umeå University, Umeå, Sweden.

    • Dmitry Shungin
  21. Centre of Excellence for Public Health, Queens University Belfast, Belfast, UK.

    • Maria F Hughes
    •  & Alun Evans
  22. Laboratory of Genetics, Intramural Research Program, National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.

    • Osorio Meirelles
    •  & Ramaiah Nagaraja
  23. Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.

    • Marika Kaakinen
  24. INSERM UMR 970, Paris Cardiovascular Research Center (PARCC), Paris, France.

    • Nabila Bouatia-Naji
  25. University Paris-Descartes, Sorbonne Paris Cité, Paris, France.

    • Nabila Bouatia-Naji
  26. National Institute for Health and Welfare, Helsinki, Finland.

    • Kati Kristiansson
    • , Aki S Havulinna
    • , Jaana Lindström
    • , Satu Männistö
    • , Markus Perola
    • , Jarmo Virtamo
    • , Jaakko Tuomilehto
    • , Veikko Salomaa
    •  & Kari Kuulasmaa
  27. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Kati Kristiansson
    •  & Markus Perola
  28. Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, London, UK.

    • Sonia Shah
    • , Aroon D Hingorani
    • , Mika Kivimaki
    •  & Meena Kumari
  29. Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

    • Marcus E Kleber
    •  & Graciela Delgado
  30. Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA Medical Center, Torrance, California, USA.

    • Xiuqing Guo
    • , Eric Kim
    • , Xiaohui Li
    • , Jie Yao
    • , Kent D Taylor
    • , Yii-Der I Chen
    •  & Jerome I Rotter
  31. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.

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

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  33. Department of Internal Medicine, University of Lund, Malmö, Sweden.

    • Cristiano Fava
    •  & Olle Melander
  34. Department of Medicine, University of Verona, Verona, Italy.

    • Cristiano Fava
  35. Uppsala University, Uppsala Clinical Research Center, Uppsala, Sweden.

    • Niclas Eriksson
  36. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Ilja M Nolte
    • , Ahmad Vaez
    •  & Harold Snieder
  37. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Patrik K Magnusson
    •  & Nancy L Pedersen
  38. Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

    • Elias L Salfati
    • , Thomas Quertermous
    • , Themistocles L Assimes
    •  & Erik Ingelsson
  39. Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.

    • Loukianos S Rallidis
  40. Children's Hospital Oakland Research Institute, Oakland, California, USA.

    • Elizabeth Theusch
  41. Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

    • Andrew J P Smith
    • , Fotios Drenos
    •  & Phil Howard
  42. NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.

    • Kate Witkowska
    • , Helen Warren
    • , Michael R Barnes
    • , Claudia P Cabrera
    • , Mark J Caulfield
    •  & Patricia B Munroe
  43. Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.

    • Tune H Pers
    • , Tonu Esko
    • , Joel N Hirschhorn
    •  & Cameron D Palmer
  44. Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.

    • Tune H Pers
    •  & Joel N Hirschhorn
  45. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Tune H Pers
    • , Joel N Hirschhorn
    • , Sekar Kathiresan
    • , Cameron D Palmer
    • , Benjamin F Voight
    •  & Christopher Newton-Cheh
  46. Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic, Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Tune H Pers
  47. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

    • Tune H Pers
  48. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Roby Joehanes
    • , Andrew D Johnson
    • , John D Eicher
    • , Daniel Levy
    • , Honghuang Lin
    • , Christopher J O'Donnell
    •  & Ramachandran S Vasan
  49. Department of Developmental Biology and Genetics, Stanford University Medical Center, Stanford, California, USA.

    • Stuart K Kim
    •  & Hinco J Gierman
  50. Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.

    • Rick Jansen
  51. National Heart, Lung, and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, Bethesda, Maryland, USA.

    • Andrew D Johnson
    •  & John D Eicher
  52. Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.

    • Young Jin Kim
    • , Yun Kyoung Kim
    • , Young-Ah Shin
    •  & Jong-Young Lee
  53. Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Wei Zhao
  54. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • Ying Wu
    •  & Karen L Mohlke
  55. Department of Public Health Sciences, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

    • Bamidele O Tayo
    •  & Richard S Cooper
  56. Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

    • Murielle Bochud
    • , Fred Paccaud
    •  & Pascal Bovet
  57. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.

    • Devin Absher
  58. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • Linda S Adair
  59. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.

    • Najaf Amin
  60. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

    • Tomas Axelsson
    • , Johan Sundstrom
    • , Ann-Christine Syvänen
    •  & Lars Lind
  61. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy.

    • Damiano Baldassarre
    •  & Elena Tremoli
  62. Centro Cardiologico Monzino, IRCCS, Milan, Italy.

    • Damiano Baldassarre
    •  & Elena Tremoli
  63. INSERM U1018, Centre for Research in Epidemiology and Population Health, University Paris-Sud, URMS 1018, Villejuif, France.

    • Beverley Balkau
  64. Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.

    • Stefania Bandinelli
  65. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.

    • Inês Barroso
    • , John Danesh
    • , Sarah Edkins
    •  & N William Rayner
  66. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Inês Barroso
  67. NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Inês Barroso
  68. School of Life Science, University of Lincoln, Joseph Banks Laboratories, Lincoln, UK.

    • Stephen Bevan
  69. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    • , Richard A Jensen
    •  & Bruce M Psaty
  70. Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
  71. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Lori L Bonnycastle
    • , Peter S Chines
    • , Francis S Collins
    • , Narisu Narisu
    •  & Amy J Swift
  72. Department of Biological Psychology, VU University, Amsterdam, the Netherlands.

    • Dorret I Boomsma
    •  & Jouke-Jan Hottenga
  73. Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.

    • Stefan R Bornstein
    •  & Peter E H Schwarz
  74. Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London, UK.

    • Morris J Brown
  75. Nephrology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

    • Michel Burnier
  76. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • John C Chambers
    • , Evangelos Evangelou
    • , He Gao
    • , Weihua Zhang
    •  & Paul Elliott
  77. Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.

    • John C Chambers
    • , Jaspal S Kooner
    •  & Weihua Zhang
  78. Imperial College Healthcare NHS Trust, London, UK.

    • John C Chambers
    •  & Jaspal S Kooner
  79. National Institute of Cancer Research, National Health Research Institutes, Zhunan Town, Taiwan.

    • I-Shou Chang
  80. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

    • Ching-Yu Cheng
    •  & Tien Y Wong
  81. Duke-NUS Graduate Medical School Singapore, Singapore.

    • Ching-Yu Cheng
    • , E-Shyong Tai
    •  & Tien Y Wong
  82. Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.

    • Ching-Yu Cheng
    •  & Tien Y Wong
  83. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan Town, Taiwan.

    • Ren-Hua Chung
    •  & Chao A Hsiung
  84. University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.

    • John M Connell
  85. Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany.

    • Angela Döring
    •  & H-Erich Wichmann
  86. Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.

    • Angela Döring
    •  & Annette Peters
  87. INSERM UMR 1167, Lille 2 University, Institut Pasteur Lille, Lille, France.

    • Jean Dallongeville
  88. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • John Danesh
  89. NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • John Danesh
  90. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Ulf de Faire
    •  & Bruna Gigante
  91. BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

    • Anna F Dominiczak
  92. Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, UK.

    • Fotios Drenos
  93. Cardiovascular Epidemiology and Genetics, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.

    • Roberto Elosua
  94. Department of Immunology, Genetics and Pathology, University of Uppsala, Biomedical Center, Uppsala, Sweden.

    • Stefan Enroth
    •  & Ulf Gyllensten
  95. Science for Life Laboratory, University of Uppsala, Biomedical Center, Uppsala, Sweden.

    • Stefan Enroth
    •  & Ulf Gyllensten
  96. Institut für Integrative und Experimentelle Genomik, Universiät zu Lübeck, Lübeck, Germany.

    • Jeanette Erdmann
  97. Deutsches Zentrum für Herz Kreislauf Forschung (DZHK), partner site Hamburg, Lübeck, Kiel, Germany.

    • Jeanette Erdmann
  98. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Andres Metspalu
    •  & Markus Perola
  99. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Tonu Esko
    • , Gulum Kosova
    •  & Christopher Newton-Cheh
  100. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.

    • Evangelos Evangelou
  101. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

    • Tove Fall
    •  & Erik Ingelsson
  102. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

    • Martin Farrall
    • , Anuj Goel
    •  & Hugh Watkins
  103. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

    • Janine F Felix
    • , Oscar H Franco
    • , Albert Hofman
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  104. Toulouse University School of Medicine, Rangueil University Hospital, INSERM UMR 1027, Toulouse, France.

    • Jean Ferrières
  105. Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Luigi Ferrucci
    •  & Toshiko Tanaka
  106. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Myriam Fornage
  107. Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica.

    • Terrence Forrester
    •  & Colin A McKenzie
  108. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • Nora Franceschini
  109. Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

    • Anders Franco-Cereceda
  110. Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

    • Ross M Fraser
    •  & James F Wilson
  111. Synpromics, Ltd, Edinburgh, UK.

    • Ross M Fraser
  112. Department of Cardiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

    • Santhi K Ganesh
  113. Epidemiology and Preventive Medicine (EPIMED) Research Centre, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.

    • Francesco Gianfagna
  114. Department of Epidemiology and Prevention, IRCCS, Istituto Neurologico Mediterraneo (NEUROMED), Pozzilli, Italy.

    • Francesco Gianfagna
  115. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Alison H Goodall
    •  & Nilesh J Samani
  116. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.

    • Alison H Goodall
    •  & Nilesh J Samani
  117. Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Mark O Goodarzi
  118. Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.

    • Mathias Gorski
  119. Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.

    • Mathias Gorski
  120. Division of Pathobiochemistry, Department of Medicine III, Technische Universität Dresden, Dresden, Germany.

    • Jürgen Gräßler
  121. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Christopher J Groves
    • , Mark I McCarthy
    •  & N William Rayner
  122. Icelandic Heart Association, Kopavogur, Iceland.

    • Vilmundur Gudnason
    • , Albert V Smith
    •  & Philippe Froguel
  123. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Vilmundur Gudnason
    • , Albert V Smith
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  124. Institute of Clinical Medicine/Obstetrics and Gynaecology, University of Oulu, Oulu, Finland.

    • Anna-Liisa Hartikainen
  125. Medical Research Center, Oulu University Hospital, Oulu, Finland.

    • Anna-Liisa Hartikainen
  126. Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.

    • Maija Hassinen
    • , Pirjo Komulainen
    • , Timo A Lakka
    •  & Rainer Rauramaa
  127. Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.

    • Caroline Hayward
    • , Veronique Vitart
    •  & James F Wilson
  128. UREN, INSERM U557, INRA U1125, CNAM, SMBH, Sorbonne Paris Cité, Université Paris 13, Bobigny, France.

    • Serge Hercberg
  129. Institute of Biomedicine, University of Oulu, Medical Research Center Oulu and Oulu University Hospital, Oulu, Finland.

    • Karl-Heinz Herzig
  130. Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Karl-Heinz Herzig
    • , Sylvain Sebert
    •  & Marjo-Riitta Jarvelin
  131. Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.

    • Karl-Heinz Herzig
  132. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated institute of the University of Lübeck, Lübeck, Germany).

    • Andrew A Hicks
    •  & Peter P Pramstaller
  133. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Joel N Hirschhorn
  134. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

    • Albert Hofman
  135. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.

    • Jostein Holmen
    • , Oddgeir Lingaas Holmen
    • , Kirsti Kvaløy
    •  & Kristian Hveem
  136. St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.

    • Oddgeir Lingaas Holmen
  137. Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, Utah, USA.

    • Steven C Hunt
  138. Department of Genetic Medicine, Weill Cornell Medical College Qatar, Doha, Qatar.

    • Steven C Hunt
  139. Department of Radiology, Erasmus MC, Rotterdam, the Netherlands.

    • M Arfan Ikram
  140. Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

    • M Arfan Ikram
  141. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.

    • Thomas Illig
    •  & Norman Klopp
  142. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.

    • Thomas Illig
    •  & Norman Klopp
  143. Hannover Medical School, Institute for Human Genetics, Hanover, Germany.

    • Thomas Illig
  144. Division of Research, Kaiser Permanente, Oakland, California, USA.

    • Carlos Iribarren
  145. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Richard A Jensen
  146. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.

    • Mika Kähönen
  147. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.

    • Mika Kähönen
    •  & Christopher Newton-Cheh
  148. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Sekar Kathiresan
    •  & Gulum Kosova
  149. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Sekar Kathiresan
    • , Gulum Kosova
    •  & Christopher Newton-Cheh
  150. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Sekar Kathiresan
  151. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Sekar Kathiresan
    •  & Christopher J O'Donnell
  152. Division of Transplantation, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Brendan J Keating
  153. Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Brendan J Keating
  154. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.

    • Kay-Tee Khaw
  155. 1st Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece.

    • Genovefa Kolovou
  156. National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, London, UK.

    • Jaspal S Kooner
  157. Department of Medicine, Children's Hospital Oakland Research Institute, Oakland, California, USA.

    • Ronald M Krauss
  158. MRC Unit for Lifelong Health and Ageing at UCL, London, UK.

    • Diana Kuh
    •  & Andrew Wong
  159. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Zoltan Kutalik
  160. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Zoltan Kutalik
  161. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

    • Johanna Kuusisto
    •  & Markku Laakso
  162. Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio, Finland.

    • Timo A Lakka
  163. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.

    • Timo A Lakka
    • , Sylvain Sebert
    •  & Rainer Rauramaa
  164. Office of Population Studies Foundation, Inc., Talamban, Cebu City, Philippines.

    • Nanette R Lee
  165. Department of Anthropology, Sociology and History, University of San Carlos, Talamban, Cebu City, Philippines.

    • Nanette R Lee
  166. Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

    • I-Te Lee
    •  & Wayne H-H Sheu
  167. School of Medicine, National Yang-Ming University, Taipei, Taiwan.

    • I-Te Lee
    •  & Wayne H-H Sheu
  168. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.

    • Wen-Jane Lee
  169. Population Sciences Branch, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Daniel Levy
  170. Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

    • Kae-Woei Liang
  171. Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.

    • Kae-Woei Liang
  172. Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Honghuang Lin
  173. European Genomic Institute for Diabetes (EGID), Lille, France.

    • Stéphane Lobbens
    • , Loic Yengo
    •  & Philippe Froguel
  174. CNRS UMR 8199, Lille Pasteur Institute, Lille, France.

    • Stéphane Lobbens
    • , Loic Yengo
    •  & Philippe Froguel
  175. Lille 2 University, Lille, France.

    • Stéphane Lobbens
    • , Loic Yengo
    •  & Philippe Froguel
  176. Center for Evidence-Based Healthcare, University of Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.

    • Gabriele Müller
  177. Department of Medicine I, University Hospital Großhadern, Ludwig Maximilians University, Munich, Germany.

    • Martina Müller-Nurasyid
  178. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians Universität, Munich, Germany.

    • Martina Müller-Nurasyid
    •  & H-Erich Wichmann
  179. Neurology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.

    • Hugh S Markus
  180. Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.

    • Eirini Marouli
    •  & George Dedoussis
  181. INSERM U1142, LIMICS, UMRS 1142, Sorbonne Universités, UPMC Université Paris 06, Université Paris 13, Paris, France.

    • Pierre Meneton
  182. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Cristina Menni
    •  & Tim D Spector
  183. Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.

    • Vladan Mijatovic
  184. Department of Medicine, Kuopio University Hospital, Kuopio, Finland.

    • Leena Moilanen
  185. Unit of General Practice, Oulu University Hospital, Oulu, Finland.

    • Leena Moilanen
  186. Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • May E Montasser
    •  & Afshin Parsa
  187. Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Alanna C Morrison
  188. Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monseratto, Monserrato, Cagliari, Italy.

    • Antonella Mulas
    •  & Serena Sanna
  189. Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland.

    • Kjell Nikus
  190. Department of Cardiology, University of Tampere School of Medicine, Tampere, Finland.

    • Kjell Nikus
  191. National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences, Bethesda, Maryland, USA.

    • Christopher J O'Donnell
    •  & Jacques Rossouw
  192. Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

    • Paul F O'Reilly
  193. Genetics and Program in Genomics, Children's Hospital Boston, Boston, Massachusetts, USA.

    • Cameron D Palmer
  194. Department of Psychiatry, EMGO Institute, Neuroscience Campus, VU University Medical Centre, Amsterdam, the Netherlands.

    • Brenda W Penninx
    •  & Johannes H Smit
  195. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Brenda W Penninx
  196. Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands.

    • Brenda W Penninx
  197. International Centre for Circulatory Health, Imperial College London, London, UK.

    • Neil Poulter
    •  & Peter Sever
  198. Department of Neurology, General Central Hospital, Bolzano, Italy.

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

    • Peter P Pramstaller
  200. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

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

    • Bruce M Psaty
  202. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.

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

    • Dabeeru C Rao
  204. Center for Non-Communicable Diseases, Karachi, Pakistan.

    • Asif Rasheed
    •  & Danish Saleheen
  205. Department of Biobank Research, Umeå University, Umeå, Sweden.

    • Frida Renström
  206. Institute of Physiology, University Medicine Greifswald, Greifswald, Germany.

    • Rainer Rettig
  207. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Kenneth M Rice
  208. University of Ottawa Heart Institute, Cardiovascular Research Methods Centre Ontario, Ottawa, Ontario, Canada.

    • Robert Roberts
  209. Ruddy Canadian Cardiovascular Genetics Centre, Ottawa, Ontario, Canada.

    • Robert Roberts
  210. South Karelia Central Hospital, Lappeenranta, Finland.

    • Jouko Saramies
  211. Deutsches Herzzentrum München, Munich, Germany.

    • Heribert Schunkert
  212. Technische Universität München, Munich, Germany.

    • Heribert Schunkert
  213. Deutsches Zentrum für Herz Kreislauf Forschung (DZHK), Munich, Germany.

    • Heribert Schunkert
  214. Munich Heart Alliance, Munich, Germany.

    • Heribert Schunkert
  215. Center For Lifecourse Health Research, University of Oulu, Oulu, Finland.

    • Sylvain Sebert
    •  & Marjo-Riitta Jarvelin
  216. College of Medicine, National Defense Medical Center, Taipei, Taiwan.

    • Wayne H-H Sheu
  217. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

    • Xueling Sim
    •  & E-Shyong Tai
  218. University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

    • Alena Stančáková
  219. Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.

    • Alice V Stanton
  220. Department of Haematology, University of Cambridge, Cambridge, UK.

    • Kathleen E Stirrups
  221. Department of Medicine, National University of Singapore and National University Health System, Singapore.

    • E-Shyong Tai
  222. Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.

    • Kirill V Tarasov
    •  & Edward G Lakatta
  223. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

    • Alexander Teumer
  224. Department of Health Sciences, University of Leicester, Leicester, UK.

    • Martin D Tobin
    •  & Louise V Wain
  225. Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.

    • Andre G Uitterlinden
  226. Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

    • Matti Uusitupa
  227. Research Unit, Kuopio University Hospital, Kuopio, Finland.

    • Matti Uusitupa
  228. Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

    • Ahmad Vaez
  229. Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

    • Dhananjay Vaidya
  230. Centre of Medical Systems Biology (CMSB 1-2), NGI Erasmus Medical Center, Rotterdam, the Netherlands.

    • Cornelia M van Duijn
  231. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.

    • Erik P A van Iperen
  232. Durrer Center for Cardiogenetic Research, ICIN–Netherlands Heart Institute, Utrecht, the Netherlands.

    • Erik P A van Iperen
  233. Section of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Ramachandran S Vasan
  234. Cardiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Ramachandran S Vasan
  235. Department of Systems Pharmacology and Translational Therapeutics, Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Benjamin F Voight
  236. Department of Internal Medicine, University Hospital Lausanne, Lausanne, Switzerland.

    • Peter Vollenweider
  237. Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Strasbourg, France.

    • Aline Wagner
  238. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.

    • Alan B Weder
    •  & Cristen J Willer
  239. University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Harm-Jan Westra
  240. Epidemiology Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica.

    • Rainford Wilks
  241. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.

    • Tom Wilsgaard
    •  & Inger Njølstad
  242. Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.

    • Tom Wilsgaard
    •  & Inger Njølstad
  243. MRC Cancer Unit, University of Cambridge, Cambridge, UK.

    • Tsun-Po Yang
  244. Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.

    • Xiaofeng Zhu
  245. Ministry of Health, Victoria, Seychelles.

    • Pascal Bovet
  246. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Danish Saleheen
  247. MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

    • Paul Elliott
    •  & Marjo-Riitta Jarvelin
  248. Enterprise Informatics, Illumina, Inc., Santa Clara, California, USA.

    • Hinco J Gierman
  249. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Cristen J Willer
  250. Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

    • Lude Franke
  251. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.

    • G Kees Hovingh
  252. Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany.

    • Peter E H Schwarz
  253. German Center for Diabetes Research (DZD), Neuherberg, Germany.

    • Peter E H Schwarz
  254. Department of Medicine, Central Finland Health Care District, Jyväskylä, Finland.

    • Juha Saltevo
  255. Dasman Diabetes Institute, Dasman, Kuwait.

    • Jaakko Tuomilehto
  256. Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.

    • Jaakko Tuomilehto
  257. Centre for Vascular Prevention, Danube University Krems, Krems, Austria.

    • Jaakko Tuomilehto
  258. Department of Medicine, Columbia University, New York, New York, USA.

    • Walter Palmas
  259. Synlab Academy, Synlab Services, Mannheim, Germany.

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

    • Winfried März
  261. Unit of Primary Care, Oulu University Hospital, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  262. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

    • Paul W Franks
  263. Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany.

    • H-Erich Wichmann
  264. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York,, New York, USA.

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

    • Ruth J F Loos
  266. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.

    • Panos Deloukas
  267. Department of Biostatistics, University of Liverpool, Liverpool, UK

    • Andrew P Morris

Consortia

  1. CHARGE-EchoGen Consortium

    A list of members and affiliations appears in the Supplementary Note.

  2. CHARGE-HF Consortium

    A list of members and affiliations appears in the Supplementary Note.

  3. Wellcome Trust Case Control Consortium

    A list of members and affiliations appears in the Supplementary Note.

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Contributions

Analysis group. Design of secondary analyses: G.B.E., T. Ferreira, T.J., A.P.M., P.B.M., C.N.-C. Computation of secondary analyses: G.B.E., T. Ferreira, T.J., A.P.M., P.B.M., C.N.-C. Manuscript writing: A.C., G.B.E., T. Ferreira, T.J., A.P.M., P.B.M., C.N.-C. Study management: P.B.M., C.N.-C.

Cardio-MetaboChip or new GWAS. WGHS. Study phenotyping: P.M.R., D.I.C., L.M.R. Genotyping or analysis: P.M.R., D.I.C., L.M.R., F. Giulianini. Study PI: P.M.R. JUPITER. Study phenotyping: P.M.R., D.I.C., L.M.R. Genotyping or analysis: D.I.C., L.M.R., F. Giulianini. Study PI: P.M.R., D.I.C. deCODE. Study phenotyping: G.B. Genotyping or analysis: G.T. Study PI: K.S., U.T. GoDARTS. Study phenotyping: C.N.A.P., L.A.D., A.D.M., A.S.F.D. Genotyping or analysis: C.N.A.P., L.A.D., A.D.M., M.I.M., C.J.G., N.W.R. Study PI: C.N.A.P., A.D.M. KORA F3/F4. Study phenotyping: A.D., H. Schunkert, J.E. Genotyping or analysis: A.-K.P., M.M.-N., N.K., T.I. Study PI: H.-E.W., A. Peters. GLACIER. Study phenotyping: F.R., G.H. Genotyping or analysis: P.W.F., D. Shungin, I.B., S. Edkins, F.R. Study PI: P.W.F. B58C. Genotyping or analysis: S. Kanoni, K.E.S., Wellcome Trust Case Control Consortium, E.M., T. Ferreira, T.J. Study PI: P.D. MORGAM. Study phenotyping: K. Kuulasmaa, F. Gianfagna, A. Wagner, J. Dallongeville. Genotyping or analysis: M.F.H., F. Gianfagna. Study PI: J.V., J.F., A.E. SardiNIA. Study phenotyping: E.G.L. Genotyping or analysis: E.G.L., O. Meirelles, S. Sanna, R.N., A. Mulas, K.V.T. NFBC1986. Study phenotyping: M.-R.J., S. Sebert, K.-H.H., A.-L.H. Genotyping or analysis: M. Kaakinen, A.-L.H. Study PI: M.-R.J. DESIR. Genotyping or analysis: N.B.-N., L.Y., S.L. Study PI: P.F., N.B.-N., B.B. DILGOM. Study phenotyping: S.M. Genotyping or analysis: K. Kristiansson, M.P., A.S.H. Study PI: V.S. IMPROVE. Study phenotyping: D.B. Genotyping or analysis: R.J.S., K.G. Study PI: A. Hamsten, E. Tremoli. HyperGEN. Study phenotyping: S.C.H., D.C.R. Genotyping or analysis: A.C., V.P., G.B.E. Study PI: S.C.H. FENLAND (MetaboChip). Study phenotyping: R.J.F.L., J. Luan, N.J.W., K.K.O. Genotyping or analysis: R.J.F.L., J. Luan, N.J.W., K.K.O. Study PI: N.J.W. Whitehall II. Study phenotyping: M. Kumari. Genotyping or analysis: M. Kumari, S. Shah, C.L. Study PI: A.D.H., M. Kivimaki. LURIC. Genotyping or analysis: M.E.K., G. Delgado. Study PI: W.M. MESA. Study phenotyping: W.P. Genotyping or analysis: W.P., X.G., J.Y., D.V., K.D.T., J.I.R., Y.-D.C. Study PI: W.P. HUNT2. Study phenotyping: K. Kvaløy, J.H., O.L.H. Genotyping or analysis: A.U.J. Study PI: K.H. FINCAVAS. Genotyping or analysis: T.L., L.-P.L., K.N., M. Kähönen. Study PI: T.L., M. Kähönen. GenNet. Study phenotyping: R.S.C., A.B.W. Genotyping or analysis: A.C., V.P., M.X.S., D.E.A., G.B.E. Study PI: A.C., R.S.C., A.B.W. SCARFSHEEP. Study phenotyping: B.G. Genotyping or analysis: R.J.S. Study PI: A. Hamsten, U.d.F. DPS. Study phenotyping: J. Lindström. Genotyping or analysis: A.U.J., P.S.C. Study PI: J.T., M.U. DR's EXTRA. Study phenotyping: P.K. Genotyping or analysis: A.U.J., M.H. Study PI: R. Rauramaa, T.A.L. FIN-D2D 2007. Genotyping or analysis: A.U.J., L.L.B. Study PI: J. Saltevo, L.M. METSIM. Study phenotyping: H.M.S. Genotyping or analysis: A.U.J., A.S. Study PI: M.L., J.K. MDC-CVA. Study phenotyping: O. Melander. Genotyping or analysis: O. Melander, C.F. Study PI: O. Melander. BRIGHT. Study phenotyping: A.F.D., M.J.B., N.J.S., J.M.C. Genotyping or analysis: T.J., P.B.M. Study PI: M.J.C., A.F.D., M.J.B., N.J.S., J.M.C., P.B.M. NESDA. Study phenotyping: J.H.S. Genotyping or analysis: H. Snieder, I.M.N. Study PI: B.W.P. EPIC (MetaboChip). Study phenotyping: R.J.F.L., J. Luan, N.J.W. Genotyping or analysis: J. Luan, N.J.W. Study PI: N.J.W., K.-T.K. ELY. Study phenotyping: C.L., J. Luan, N.J.W. Genotyping or analysis: C.L., J. Luan, N.J.W. Study PI: N.J.W. DIAGEN. Study phenotyping: J.G., G.M. Genotyping or analysis: A.U.J., G.M. Study PI: P.E.H.S., S.R.B. GOSH. Study phenotyping: P.K.M., N.L.P. Genotyping or analysis: E.I., P.K.M., N.L.P., T. Fall. Study PI: E.I. Tromsø. Study phenotyping: T.W. Genotyping or analysis: A.U.J., A.J.S., N.N. Study PI: I.N.N. ADVANCE. Study phenotyping: T.L.A., C.I. Genotyping or analysis: T.L.A., E.L.S., T.Q. Study PI: T.L.A., T.Q., C.I. ULSAM. Study phenotyping: E.I., J. Sundstrom. Genotyping or analysis: E.I., N.E., J. Sundstrom, A.-C.S. Study PI: J. Sundstrom. PIVUS. Study phenotyping: L. Lind, J. Sundstrom. Genotyping or analysis: L. Lind, N.E., J. Sundstrom, T.A. Study PI: L. Lind, J. Sundstrom. MRC NSHD. Study phenotyping: D.K. Genotyping or analysis: A. Wong, J. Luan, D.K., K.K.O. Study PI: D.K. ASCOT. Study phenotyping: A.V. Stanton, N.P. Genotyping or analysis: T.J., M.J.C., P.B.M., E.P.A.v.I. Study PI: P.S., M.J.C. THISEAS. Genotyping or analysis: L.S.R., S. Kanoni, E.M., G. Kolovou. Study PI: G. Dedoussis, P.D. PARC. Study phenotyping: R.M.K. Genotyping or analysis: K.D.T., E. Theusch, J.I.R., X.L., M.O.G., Y.-D.I.C. Study PI: R.M.K. AMC-PAS. Genotyping or analysis: G.K.H., P.D., E.P.A.v.I. Study PI: G.K.H. CARDIOGENICS. Genotyping or analysis: S. Kanoni, A.H.G. Study PI: P.D., A.H.G., J.E., N.J.S., H. Schunkert.

Secondary analyses. Allele-specific FAIRE. Design of secondary analysis: A.J.P.S. Computation of secondary analysis: A.J.P.S., F.D., P.H. ASAP eQTL. Design of secondary analysis: A.F.-C. Computation of secondary analysis: L. Folkersen, P. Eriksson. CARDIOGENICS eQTL. Computation of secondary analysis: L. Lataniotis. Cardio-MetaboChip design. P.B.M., C.N.-C., T.J., B.F.V., H.M.K. Comprehensive literature review. Design of secondary analysis: P.B.M. Computation of secondary analysis: K.W., P.B.M. DEPICT. Design of secondary analysis: L. Franke, T.H.P., J.N.H. Computation of secondary analysis: T.H.P. DHS and methylation analysis by tissue. Design of secondary analysis: C.J.W. Computation of secondary analysis: E.M.S. DHS and methylation by cell line. Design of secondary analysis: D.I.C. Computation of secondary analysis: D.I.C., F. Giulianini. FHS eSNP. Design of secondary analysis: R. Joehanes. Computation of secondary analysis: R. Joehanes. ICBP SC. C.N.-C., M.J.C., P.B.M., A.C., K.M.R., P.F.O'R., W.P., D.L., M.D.T., B.M.P., A.D.J., P. Elliott, C.M.v.D., D.I.C., A.V. Smith, M. Bochud, L.V.W., H. Snieder, G.B.E. Kidney eQTL. Computation of secondary analysis: H.J.G., S.K.K. MAGENTA. Design of secondary analysis: D.I.C. Computation of secondary analysis: D.I.C. Miscellaneous. Computation of secondary analysis: H. Warren. MuTHER eQTL. Design of secondary analysis: P.D. Computation of secondary analysis: L. Lataniotis, T.-P.Y. NESDA eQTL. Design of secondary analysis: R. Jansen. Computation of secondary analysis: R. Jansen, A.V. NTR eQTL. Design of secondary analysis: R. Jansen. Computation of secondary analysis: R. Jansen, J.-J.H. Study PI: D.I.B. eQTL, EGCUT. Design of secondary analysis: A. Metspalu. Computation of secondary analysis: T.E., A. Metspalu. eQTL, Groningen. Design of secondary analysis: L. Franke. Computation of secondary analysis: H.-J.W., L. Franke. Public eSNP and methylation. Design of secondary analysis: A.D.J., J.D.E. Computation of secondary analysis: A.D.J., J.D.E. PubMed search. Design of secondary analysis: G.B.E. Computation of secondary analysis: G.B.E., L. Lin. WGHS conditional. Design of secondary analysis: D.I.C. Computation of secondary analysis: D.I.C., F. Giulianini, L.M.R.

Lookup of Cardio-MetaboChip variants. HEXA. Genotyping or analysis: Y.J.K., Y.K.K., Y.-A.S. Study PI: J.-Y.L. RACe. Study phenotyping: D. Saleheen, W. Zhao, A.R. Genotyping or analysis: W. Zhao, A.R. Study PI: D. Saleheen. HALST. Study phenotyping: C.A.H. Genotyping or analysis: J.I.R., Y.-D.C., C.A.H., R.-H.C., I.-S.C. Study PI: C.A.H. CLHNS. Study phenotyping: N.R.L., L.S.A. Genotyping or analysis: Y.W., N.R.L., L.S.A. Study PI: K.L.M., L.S.A. GxE/Spanish Town. Study phenotyping: B.O.T., C.A.M., R.W. Genotyping or analysis: C.D.P. Study PI: R.S.C., C.A.M., R.W., T. Forrester, J.N.H. DRAGON. Study phenotyping: W.-J.L., W.H.-H.S., K.-W.L., I.-T.L. Genotyping or analysis: J.I.R., Y.-D.C., E.K., D.A., K.D.T., X.G. Study PI: W.H.-H.S. SEY: study phenotyping: P.B. Genotyping or analysis: M. Bochud, G.B.E., F.M. Study PI: P.B., M. Bochud, M. Burnier, F.P. TUDR: study phenotyping: W.H.-H.S., I.-T.L., W.-J.L. Genotyping or analysis: J.I.R., Y.-D.C., E.K., K.D.T., X.G. Study PI: W.H.-H.S. TANDEM. Study phenotyping: P.B., M. Bochud. Genotyping or analysis: G.B.E., F.M. Study PI: P.B., M. Bochud, M. Burnier, F.P.

Imputed genotypes. FHS. Study phenotyping: D.L. Genotyping or analysis: D.L. Study PI: D.L. ARIC. Study phenotyping: E.B. Genotyping or analysis: G.B.E., E.B., A.C.M., A.C., S.K.G. Study PI: E.B., A.C. RS. Genotyping or analysis: G.C.V., A.G.U. Study PI: A. Hofman, A.G.U., O.H.F. CoLaus. Study phenotyping: P.V. Genotyping or analysis: Z.K. Study PI: P.V. NFBC1966. Study phenotyping: M.-R.J. Genotyping or analysis: P.F.O'R. Study PI: M.-R.J. SHIP. Study phenotyping: R. Rettig. Genotyping or analysis: A.T. CHS. Study phenotyping: B.M.P. Genotyping or analysis: K.M.R. Study PI: B.M.P. EPIC (GWAS). Study phenotyping: N.J.W., R.J.F.L., J. Luan. Genotyping or analysis: N.J.W., J.H.Z., J. Luan. Study PI: N.J.W., K.-T.K. SU.VI.MAX. Study phenotyping: S.H. Genotyping or analysis: S.H., P.M. Study PI: P.M. Amish. Genotyping or analysis: M.E.M. Study PI: A. Parsa. FENLAND (GWAS). Study phenotyping: N.J.W., J. Luan, R.J.F.L., K.K.O. Genotyping or analysis: N.J.W., J. Luan, R.J.F.L., K.K.O. Study PI: N.J.W. DGI. Study phenotyping: C.N.-C. Genotyping or analysis: C.N.-C., G. Kosova. Study PI: C.N.-C. ERF (EUROSPAN). Genotyping or analysis: N.A. Study PI: C.M.v.D. MIGEN. Study phenotyping: S. Kathiresan, R.E. Genotyping or analysis: S. Kathiresan, R.E. Design of secondary analysis: S. Kathiresan, R.E. MICROS. Study phenotyping: P.P.P. Genotyping or analysis: A.A.H. Study PI: A.A.H., P.P.P. FUSION. Genotyping or analysis: A.U.J. Study PI: M. Boehnke, F.S.C., K.L.M., J. Saramies. TwinsUK. Genotyping or analysis: C.M. Study PI: T.D.S. PROCARDIS. Genotyping or analysis: M. Farrall, A.G. Study PI: M. Farrall. BLSA. Study phenotyping: L. Ferrucci. Genotyping or analysis: T.T. Study PI: L. Ferrucci. ORCADES. Study phenotyping: J.F.W. Genotyping or analysis: R.M.F. Study PI: J.F.W. Croatia-Vis. Genotyping or analysis: V.V., C.H. Study PI: V.V., C.H. NSPHS. Genotyping or analysis: S. Enroth. Study PI: U.G. InCHIANTI. Genotyping or analysis: T.T. Study PI: S. Bandinelli. AGES Reykjavik. Study phenotyping: V.G. Genotyping or analysis: A.V. Smith. Study PI: V.G.

Lookup. CARDIoGRAMplusC4D. Genotyping or analysis: P.D. Study PI: J. Danesh, H. Schunkert, T.L.A., J.E., S. Kathiresan, R. Roberts, N.J.S., P.D., H. Watkins. CHARGE cIMT. Genotyping or analysis: C.J.O'D., J.C.B. CHARGE EYE. Genotyping or analysis: T.Y.W., X.S., R.A.J. Study PI: T.Y.W. CHARGE-HF Consortium. Study phenotyping: R.S.V., J.F.F. Genotyping or analysis: H.L., J.F.F. Study PI: R.S.V. CKDGen. Genotyping or analysis: M.G., V.M. COGENT-BP. Study phenotyping: N.F., J.R. Genotyping or analysis: N.F., X.Z., B.J.K., B.O.T., J.R. EchoGen Consortium. Study phenotyping: R.S.V., J.F.F. Genotyping or analysis: H.L., J.F.F. Study PI: R.S.V. KidneyGen Consortium. Study phenotyping: J.C.C., J.S.K., P. Elliott. Genotyping or analysis: W. Zhang, J.C.C., J.S.K. Study PI: J.C.C., J.S.K. MetaStroke. Genotyping or analysis: S. Bevan, H.S.M. NeuroCHARGE. Genotyping or analysis: M. Fornage, M.A.I. Study PI: M.A.I. PROMIS. Study phenotyping: D. Saleheen, W. Zhao, J. Danesh. Genotyping or analysis: W. Zhao. Study PI: D. Saleheen. SEED. Study phenotyping: T.Y.W., C.-Y.C. Genotyping or analysis: E.-S.T., C.-Y.C., C.-Y.C. Study PI: C.-Y.C., T.Y.W. UK Biobank. BP group leaders: M.J.C., P. Elliott. Genotyping or analysis: M.R.B., H. Warren, C.P.C., E.E., H.G.

Competing interests

I.B. owns stock in Incyte and GlaxoSmithKline. A.C. is a paid member of the Scientific Advisory Board of Biogen Idec. These potential conflicts of interest are managed by the policies of Johns Hopkins University School of Medicine. D.I.C. receives genotyping and collaborative scientific support from Amgen and receives support for genetic analysis from AstraZeneca. J.F.F. worked until 2013 in ErasmusAGE, a center for ageing research across the life course funded by Nestlé Nutrition (Nestec, Ltd), Metagenics, Inc., and AXA. H.J.G. currently works for Illumina. T.J. is an employee of and owns stock in GlaxoSmithKline. B.M.P. serves on the DSMB for a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee for the Yale Open Data Access Project funded by Johnson & Johnson. P.M.R. receives genotyping and collaborative scientific support from Amgen and receives support for genetic analysis from AstraZeneca. N.P. has received financial support from several pharmaceutical companies that manufacture blood pressure–lowering or lipid-lowering agents, or both, and consultancy fees. P.S. has received research awards from Pfizer. M.J.C. is Chief Scientist for Genomics England, a UK government company.

Corresponding authors

Correspondence to Christopher Newton-Cheh or Patricia B Munroe.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Note and Supplementary Figures 1–10.

Excel files

  1. 1.

    Supplementary Table 1

    Individual cohort study information and blood pressure measurement methods.

  2. 2.

    Supplementary Table 2

    Genotyping methods.

  3. 3.

    Supplementary Table 3

    Data type contribution and participant characteristics.

  4. 4.

    Supplementary Table 4

    Meta-analysis stage 4 results.

  5. 5.

    Supplementary Table 5

    UK-CardioMetabolic Consortium validation.

  6. 6.

    Supplementary Table 6

    Loci identified by GCTA with multiple signals of association.

  7. 7.

    Supplementary Table 7

    All SNPs selected by GCTA as independently associated with SBP.

  8. 8.

    Supplementary Table 8

    All SNPs selected by GCTA as independently associated with DBP.

  9. 9.

    Supplementary Table 9

    List of SNPs at genome-wide significant Cardio-MetaboChip loci for secondary analyses.

  10. 10.

    Supplementary Table 10

    Conditional analysis using the WGHS data set.

  11. 11.

    Supplementary Table 11

    Summary of Cardio-MetaboChip blood pressure fine-mapping regions.

  12. 12.

    Supplementary Table 12

    Ninety-nine percent credible intervals at Cardio-MetaboChip blood pressure fine-mapping regions.

  13. 13.

    Supplementary Table 13

    Ninety-nine percent credible causal SNPs at Cardio-MetaboChip blood pressure fine-mapping regions.

  14. 14.

    Supplementary Table 14

    eSNP analysis for cell types other than whole blood.

  15. 15.

    Supplementary Table 15

    eSNP analysis for whole blood.

  16. 16.

    Supplementary Table 16

    Analysis of enrichment of DNase-hypersensitive sites among the blood pressure loci, by cell type.

  17. 17.

    Supplementary Table 17

    Tissue categorization for DNase-hypersensitive site analyses.

  18. 18.

    Supplementary Table 18

    Analysis of enrichment of DNase-hypersensitive sites among the blood pressure loci, grouping cell types by tissue.

  19. 19.

    Supplementary Table 19

    Analysis of enrichment of methylation sites among the blood pressure loci.

  20. 20.

    Supplementary Table 20

    Blood pressure SNPs enriched in DHS sites in blood vessels.

  21. 21.

    Supplementary Table 21

    MAGENTA analysis.

  22. 22.

    Supplementary Table 22

    DEPICT analysis.

  23. 23.

    Supplementary Table 23

    FAIRE analysis.

  24. 24.

    Supplementary Table 24

    Non-European meta-analysis.

  25. 25.

    Supplementary Table 25

    Detailed results of risk score analyses for each SNP.

  26. 26.

    Supplementary Table 26

    Genetic blood pressure risk score analysis applied to related cardiovascular phenotypes.

  27. 27.

    Supplementary Table 27

    Genes at new blood pressure loci using DEPICT.

CSV files

  1. 1.

    Supplementary Data

    Cardio-MetaboChip blood pressure association statistics (P values). Full results can be obtained via dbGaP.

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DOI

https://doi.org/10.1038/ng.3667

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