Letter | Published:

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Nature Genetics volume 43, pages 10051011 (2011) | Download Citation

Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans1,2,3. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10−8 to P = 2.3 × 10−13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

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Acknowledgements

A number of the participating studies and authors are members of the CHARGE and Global BPgen consortia. Many funding mechanisms by the US National Institutes of Health and National Heart, Lung, and Blood Institute, European and private funding agencies contributed to this work, and a full list of acknowledgements is provided in the Supplementary Note.

Author information

Author notes

    • Louise V Wain
    • , Germaine C Verwoert
    • , Paul F O'Reilly
    • , Gang Shi
    • , Toby Johnson
    • , Patricia B Munroe
    • , Bruce M Psaty
    • , Mark J Caulfield
    • , Dabeeru C Rao
    • , Martin D Tobin
    • , Paul Elliott
    •  & Cornelia M van Duijn

    These authors contributed equally to this work.

Affiliations

  1. Department of Health Sciences, University of Leicester, Leicester, UK.

    • Louise V Wain
    •  & Martin D Tobin
  2. Department of Genetics, University of Leicester, Leicester, UK.

    • Louise V Wain
    •  & Martin D Tobin
  3. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Germaine C Verwoert
    • , Francesco U S Mattace-Raso
    • , Fernando Rivadeneira
    • , Eric J G Sijbrands
    •  & Andre G Uitterlinden
  4. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), The Netherlands.

    • Germaine C Verwoert
    • , Fernando Rivadeneira
    • , Andre G Uitterlinden
    • , Janine F Felix
    • , Jacqueline C M Witteman
    •  & Cornelia M van Duijn
  5. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • Paul F O'Reilly
    • , John C Chambers
    • , Weihua Zhang
    • , Xinzhong Li
    • , Marjo-Riitta Jarvelin
    •  & Paul Elliott
  6. Division of Biostatistics, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, USA.

    • Gang Shi
    •  & Dabeeru C Rao
  7. Department of Genetics, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, USA.

    • Gang Shi
    •  & Dabeeru C Rao
  8. Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Toby Johnson
    • , Patricia B Munroe
    •  & Mark J Caulfield
  9. Framingham Heart Study, Framingham, Massachusetts, USA.

    • Andrew D Johnson
    • , Martin G Larson
    • , Shih-Jen Hwang
    • , Ramachandran S Vasan
    • , Thomas J Wang
    •  & Daniel Levy
  10. National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

    • Andrew D Johnson
    • , Shih-Jen Hwang
    •  & Daniel Levy
  11. Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

    • Murielle Bochud
  12. University of Lausanne, Lausanne, Switzerland.

    • Murielle Bochud
  13. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Kenneth M Rice
  14. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

    • Peter Henneman
    • , Peter A C 't Hoen
    •  & Ko Willems van Dijk
  15. Icelandic Heart Association, Kopavogur, Iceland.

    • Albert V Smith
    • , Thor Aspelund
    • , Valur Emilsson
    •  & Vilmundur Gudnason
  16. University of Iceland, Reykajvik, Iceland.

    • Albert V Smith
    • , Thor Aspelund
    •  & Vilmundur Gudnason
  17. 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
    •  & Aravinda Chakravarti
  18. Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.

    • Georg B Ehret
  19. Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Geneva, Switzerland.

    • Georg B Ehret
  20. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Najaf Amin
    • , A Cecile J W Janssens
    • , Albert Hofman
    • , Suman Kundu
    • , Francesco U S Mattace-Raso
    • , Eric J G Sijbrands
    • , Yurii Aulchenko
    • , Janine F Felix
    • , Monique Breteler
    • , Jacqueline C M Witteman
    •  & Cornelia M van Duijn
  21. Department of Mathematics, Boston University, Boston, Massachusetts, USA.

    • Martin G Larson
  22. Genetics Division R&D, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.

    • Vincent Mooser
  23. Division of Community Health Sciences, St George's, University of London, London, UK.

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

    • David Hadley
  25. Department of Internal Medicine B, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Marcus Dörr
  26. Cardiovascular Health Research Unit, Division of Internal Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    • , David Siscovick
    •  & Bruce M Psaty
  27. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Tõnu Esko
    • , Helene Alavere
    • , Toomas Haller
    • , Aime Keis
    • , Mari-Liis Tammesoo
    •  & Andres Metspalu
  28. Estonian Biocenter, Tartu, Estonia.

    • Tõnu Esko
    •  & Andres Metspalu
  29. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Tõnu Esko
    • , Maris Laan
    • , Elin Org
    • , Siim Sõber
    •  & Andres Metspalu
  30. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK.

    • Jing Hua Zhao
    • , Jian'an Luan
    • , Ruth J F Loos
    •  & Nicholas J Wareham
  31. Centre National de Génotypage, Commissariat à L'Energie Atomique, Institut de Génomique, Evry, France.

    • Simon Heath
    •  & Mark Lathrop
  32. Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Jingyuan Fu
    • , Behrooz Z Alizadeh
    • , Xiaowen Lu
    • , Ilja M Nolte
    •  & Harold Snieder
  33. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Jingyuan Fu
  34. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.

    • Giorgio Pistis
    • , Tanguy Corre
    • , Corrado Masciullo
    • , Cinzia Sala
    •  & Daniela Toniolo
  35. Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Pankaj Arora
    •  & Christopher Newton-Cheh
  36. Cardiovascular Epidemiology and Genetics, Institut Municipal d'Investigacio Medica, Barcelona Biomedical Research Park, Barcelona, Spain.

    • Gavin Lucas
  37. Institute for Maternal and Child Health–Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) 'Burlo Garofolo'—Trieste, University of Trieste, Trieste, Italy.

    • Nicola Pirastu
    • , Adamo Pio d'Adamo
    •  & Paolo Gasparini
  38. Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy. Affiliated Institute of the University of Lübeck, Lübeck, Germany.

    • Irene Pichler
    • , Fabiola Del Greco M
    • , Maurizio Facheris
    •  & Arne Pfeufer
  39. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Anne U Jackson
    • , Jennifer L Bragg-Gresham
    • , Michael Boehnke
    •  & Goncalo R Abecasis
  40. Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, Western Australia, Australia.

    • Rebecca J Webster
    •  & Lyle J Palmer
  41. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Feng Zhang
    • , Massimo Mangino
    • , So-Youn Shin
    • , Nicole Soranzo
    •  & Tim D Spector
  42. Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • John F Peden
    • , Hugh Watkins
    • , Anuj Goel
    • , Halit Ongen
    •  & Martin Farrall
  43. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK.

    • John F Peden
    • , Hugh Watkins
    • , Anuj Goel
    •  & Martin Farrall
  44. Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.

    • Helena Schmidt
    • , Pierre Gider
    •  & Marion Zeginigg
  45. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
    • , Yuri Milaneschi
    •  & Luigi Ferrucci
  46. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

    • Harry Campbell
    • , Sarah H Wild
    • , Igor Rudan
    •  & James F Wilson
  47. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

    • Wilmar Igl
    •  & Ulf B Gyllensten
  48. Neuroscience Campus Amsterdam (NCA), Department of Biological Psychology, VU University, Amsterdam, The Netherlands.

    • Jouke-Jan Hottenga
  49. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.

    • Veronique Vitart
    • , Pau Navarro
    • , Caroline Hayward
    •  & Alan F Wright
  50. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

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

    • Daniel I Chasman
    •  & Paul M Ridker
  52. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.

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

    • Stella Trompet
  54. Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.

    • John C Chambers
    • , Weihua Zhang
    •  & Jaspal S Kooner
  55. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Xiuqing Guo
    • , Kent D Taylor
    •  & Yii-Der Ida Chen
  56. Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland.

    • Terho Lehtimäki
  57. Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.

    • Brigitte Kühnel
    •  & Christian Gieger
  58. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.

    • Lorna M Lopez
    • , John M Starr
    •  & Ian J Deary
  59. Department of Psychology, The University of Edinburgh, Edinburgh, UK.

    • Lorna M Lopez
    • , Gail Davies
    •  & Ian J Deary
  60. Department of Public Health, Medical School, University of Split, Split, Croatia.

    • Ozren Polašek
  61. Department of Pharmacology, Medical School, University of Split, Split, Croatia.

    • Mladen Boban
  62. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Christopher P Nelson
    •  & Nilesh J Samani
  63. Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas at Houston Health Science Center, Houston, Texas, USA.

    • Alanna C Morrison
  64. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.

    • Santhi K Ganesh
  65. Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

    • Shih-Jen Hwang
    •  & Daniel Levy
  66. Division of Epidemiology and Prevention, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Ramachandran S Vasan
  67. Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Thomas J Wang
  68. Département de Génétique Médicale, Université de Lausanne, Lausanne, Switzerland.

    • Sven Bergmann
    •  & Jacques S Beckmann
  69. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Sven Bergmann
  70. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

    • Peter Vollenweider
    •  & Gérard Waeber
  71. Finnish Institute of Occupational Health, Oulu, Finland.

    • Jaana Laitinen
  72. National Institute of Health and Welfare, Department of Children, Young People and Families, Oulu, Finland.

    • Anneli Pouta
  73. Institute of Clinical Medicine, Obstetrics and Gynaecology, University of Oulu, Oulu, Finland.

    • Anneli Pouta
  74. Department of Physiatrics, Lapland Central Hospital, Rovaniemi, Finland.

    • Paavo Zitting
  75. Avon Longitudinal Study of Parents and Children (ALSPAC) Laboratory, Department of Social Medicine, University of Bristol, Bristol, UK.

    • Wendy L McArdle
  76. Institute of Pharmacology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Heyo K Kroemer
  77. Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Uwe Völker
  78. Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Henry Völzke
  79. Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Nicole L Glazer
  80. National Institute of Aging's Laboratory for Epidemiology, Demography and Biometry, Bethesda, Maryland, USA.

    • Tamara B Harris
  81. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.

    • Inês Barroso
    • , So-Youn Shin
    •  & Nicole Soranzo
  82. University of Cambridge Metabolic Research Labs, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Inês Barroso
  83. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.

    • Kay-Tee Khaw
  84. U557 Institut National de la Santé et de la Recherche Médicale, Paris, France.

    • Pilar Galan
    •  & Serge Hercberg
  85. U1125 Institut National de la Recherche Agronomique, Paris, France.

    • Pilar Galan
    •  & Serge Hercberg
  86. Université Paris 13, Bobigny, France.

    • Pilar Galan
    •  & Serge Hercberg
  87. Department of Statistics, Pontificia Universidad Catolica de Chile, Santiago, Chile.

    • Susana Eyheramendy
  88. Department of Psychiatry/EMGO Institute/Neuroscience Campus, VU University Medical Centre, Amsterdam, The Netherlands.

    • Brenda W Penninx
  89. Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands.

    • Brenda W Penninx
  90. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Brenda W Penninx
  91. Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, Lund University, University Hospital Malmö, Malmö, Sweden.

    • Leif Groop
  92. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Benjamin F Voight
    • , David Altshuler
    •  & Christopher Newton-Cheh
  93. Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, Malmö, Sweden.

    • Olle Melander
  94. National Heart, Lung, and Blood Institute and its Framingham Heart Study, Framingham, Massachusetts, USA.

    • Christopher J O'Donnell
  95. Department of Chronic Disease Prevention, THL-National Institute for Health and Welfare, Helsinki, Finland.

    • Veikko Salomaa
  96. Institute for Maternal and Child Health-Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS) 'Burlo Garofolo'—Trieste, Italy.

    • Antonella Fabretto
    • , Flavio Faletra
    • , Sheila Ulivi
    •  & Paolo Gasparini
  97. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Francis S Collins
  98. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Richard N Bergman
  99. Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia, Australia.

    • John P Beilby
  100. Molecular Genetics, PathWest Laboratory Medicine, Nedlands, Western Australia, Australia.

    • John P Beilby
  101. Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

    • John P Beilby
    • , Joseph Hung
    • , A William Musk
    •  & Lyle J Palmer
  102. School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.

    • Joseph Hung
  103. School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.

    • A William Musk
  104. Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

    • A William Musk
  105. Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

    • Anders Hamsten
  106. Department of Neurology Section of Special Neurology, Medical University Graz, Graz, Austria.

    • Marisa Loitfelder
    •  & Reinhold Schmidt
  107. National Institute of Aging's Laboratory of Neurogenetics, Bethesda, Maryland, USA.

    • Dena Hernandez
    •  & Andrew Singleton
  108. Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland, USA.

    • Samer S Najjar
  109. Cardiovascular Research Institute, MedStar Health Research Institute, Washington Hospital Center, Washington DC, USA.

    • Samer S Najjar
  110. Tuscany Regional Health Agency, Florence, Italy.

    • Anna Maria Corsi
  111. EMGO+ institute, Department of Biological Psychology, VU University, Amsterdam, The Netherlands.

    • Eco J C de Geus
    • , Gonneke Willemsen
    •  & Dorret I Boomsma
  112. Amgen, Cambridge, Massachusetts, USA.

    • Alex N Parker
  113. Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.

    • Brendan Buckley
  114. Institute of Cardiovascular and Medical Sciences, School of Medicine, University of Glasgow, Glasgow, UK.

    • David Stott
  115. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Monserrato, Italy.

    • Marco Orru
    •  & Manuela Uda
  116. Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Melanie M van der Klauw
  117. National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.

    • James Scott
    •  & Jaspal S Kooner
  118. Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

    • Gregory L Burke
  119. Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland.

    • Mika Kähönen
  120. Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.

    • Jorma Viikari
  121. Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.

    • Angela Döring
    •  & H-Erich Wichmann
  122. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany.

    • Angela Döring
  123. Institute of Human Genetics, Helmholtz Zentrum München–German Research Centre for Environmental Health, Neuherberg, Germany.

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

    • Thomas Meitinger
  125. Geriatric Medicine Unit, The University of Edinburgh, Royal Victoria, Edinburgh, UK.

    • John M Starr
  126. Cardiovascular Disease Franchise, Merck Research Laboratory, Rahway, New Jersey, USA.

    • Andrew Plump
  127. Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands.

    • Jan H Lindeman
  128. Leiden Genome Technology Center, Leiden University Medical Center, Leiden, The Netherlands.

    • Peter A C 't Hoen
  129. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.

    • Inke R König
    •  & Michael Preuss
  130. German Cancer Research Center, Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany.

    • Janine F Felix
  131. Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK.

    • Robert Clarke
    •  & Jemma C Hopewell
  132. Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Stéphanie Debette
  133. Boston University School of Public Health, Boston, Massachusetts, USA.

    • Anita L DeStefano
  134. Brown Foundation Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Myriam Fornage
  135. Cardiovascular Engineering, Inc., Norwood, Massachusetts, USA.

    • Gary F Mitchell
  136. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Nicholas L Smith
    • , David Siscovick
    •  & Bruce M Psaty
  137. Seattle Epidemiologic Research and Information, Center of the Department of Veterans Affairs Office of Research and Development, Seattle, Washington, USA.

    • Nicholas L Smith
  138. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.

    • Nicholas L Smith
    •  & Bruce M Psaty
  139. deCODE genetics Inc. Reykjavik, Iceland.

    • Hilma Holm
    • , Kari Stefansson
    • , Gudmar Thorleifsson
    •  & Unnur Thorsteinsdottir
  140. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Kari Stefansson
    •  & Unnur Thorsteinsdottir
  141. Leicester National Institute of Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
  142. Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany.

    • Michael Preuss
    •  & Jeanette Erdmann
  143. Croatian Centre for Global Health, University of Split Medical School, Split, Croatia.

    • Igor Rudan
  144. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität and Klinikum Grosshadern, Munich, Germany.

    • H-Erich Wichmann
  145. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and the Department of Clinical Physiology, Turku University Hospital, Turku, Finland.

    • Olli T Raitakari
  146. Columbia University, New York, New York, USA.

    • Walter Palmas
  147. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Ronald P Stolk
  148. Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands.

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

    • J Wouter Jukema
  150. Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.

    • Stefania Bandinelli
  151. Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

    • Lyle J Palmer
  152. Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.

    • Lyle J Palmer
  153. National Institute for Health and Welfare, Diabetes Prevention Unit, Helsinki, Finland.

    • Jaakko Tuomilehto
  154. Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, Finland.

    • Jaakko Tuomilehto
  155. South Ostrobothnia Central Hospital, Seinajoki, Finland.

    • Jaakko Tuomilehto
  156. Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

    • Arne Pfeufer
  157. Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.

    • Arne Pfeufer
  158. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • David Siscovick
  159. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • David Altshuler
  160. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • David Altshuler
  161. Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • David Altshuler
  162. Institute of Molecular Genetics–Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy.

    • Daniela Toniolo
  163. U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris, France.

    • Pierre Meneton
  164. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Ben A Oostra
  165. National Institute of Aging's Laboratory for Epidemiology, Demography and Biometry, Bethesda, Maryland, USA.

    • Lenore Launer
  166. Institute of Physiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.

    • Rainer Rettig
  167. Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

    • Jacques S Beckmann
  168. Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.

    • Ko Willems van Dijk
  169. Human Genetics Center, Houston, Texas, USA.

    • Eric Boerwinkle
  170. Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Paul M Ridker
  171. Institute of Health Sciences, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  172. Biocenter, University of Oulu, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  173. Department of Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  174. Department of Psychiatry, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, USA.

    • Dabeeru C Rao
  175. Department of Mathematics, Washington University in St. Louis, School of Medicine, Saint Louis, Missouri, USA.

    • Dabeeru C Rao
  176. MRC-Health Protection Agency (HPA) Centre for Environment and Health, Imperial College London, London, UK.

    • Paul Elliott
  177. Centre of Medical Systems Biology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Cornelia M van Duijn

Consortia

  1. LifeLines Cohort Study

  2. EchoGen consortium

    A full list of members is provided in the Supplementary Note.

  3. AortaGen Consortium

    A full list of members is provided in the Supplementary Note.

  4. CHARGE Consortium Heart Failure Working Group

    A full list of members is provided in the Supplementary Note.

  5. KidneyGen consortium

    A full list of members is provided in the Supplementary Note.

  6. CKDGen consortium

    A full list of members is provided in the Supplementary Note.

  7. Cardiogenics consortium

    A full list of members is provided in the Supplementary Note.

  8. CardioGram

    A full list of members is provided in the Supplementary Note.

Authors

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Contributions

ICBP-GWAS PP and MAP Working and Writing Sub-Group (alphabetical order): M.J.C., P.E. (co-chair), T.J., P.B.M., P.F.O., M.D.T. (co-chair), C.M.v.D. (co-chair), G.C.V., L.V.W. ICBP-GWAS Steering Committee (alphabetical order): G.R.A., M. Bochud, M. Boehnke, M.J.C. (co-chair), A.C., G.B.E., P.E., T.B.H., M.-R.J., A.D.J., T.J., M.G.L., L.L., D.L. (co-chair), P.B.M.(co-chair), C.N.-C. (co-chair), B.M.P., K.M.R., A.V.S., M.D.T., C.M.v.D., G.C.V. Analysis: L.V.W., G.C.V., P.F.O., T.J. Expression analyses: V.E., P.H., A.D.J., D.L., J.H.L., C.P.N., A. Plump, P.A.C.'t H., K.W.v.D. Cohort contributions (alphabetical order): Study concept/design: AGES: T.A., V.G., T.B.H., L.L., A.V.S. AortaGen Consortium: G.F.M. ARIC: E.B., A.C., S.K.G. ASPS: H. Schmidt, R.S. BLSA: L.F. B58C-T1DGC: D.P.S. B58C-WTCCC: D.P.S. BHS: L.J.P. CARDIoGRAM Consortium: N.J.S. C4D Consortium: R. Clarke, CHS: J.C.B., N.L.G., B.M.P., K.M.R., K.D.T. CHARGE Consortium Heart Failure Working Group: N.L.S. CoLaus: V.M., P. Vollenweider, G. Waeber CROATIA-Korcula: C.H. CROATIA-Split: M. Boban, I.R. CROATIA-Vis: A.F.W. DeCode Genetics: H.H., K.S., G.T., U.T. DGI controls: D.A., L.G., C.N.-C. ENGAGE: J.E., I.R.K. EGCUT: H.A., A.M. EPIC: K.-T.K. ERF: B.A.O. Fenland: N.J.W. FUSION: M. Boehnke, F.S.C., R.N.B., J.T. INGI CARL: A.P.d'A., P. Gasparini INGI-FVG: A.P.d'A., P. Gasparini INCHIANTI: S. Bandinelli., Y.M. KORA S3: C.G., M. Laan, E.O. KORA F4: T.M., H.-E.W. LifeLines: R.P.S., M.M.v.d.K. LOLIPOP: J.C.C., P.E., J.S.K. LBC1921/LBC1936: I.J.D., J.M.S. MICROS: A. Pfeufer MESA: G.L.B., X.G., W.P. MIGen controls: O.M., C.J.O., V.S., D. Siscovick NESDA: B.W.P., H. Snieder NEURO-CHARGE Consortium: M. Breteler, M. Fornage NFBC1966: M.-R.J., P.Z. NSPHS: U.B.G. NTR: D.I.B., E.J.C.d.G. ORCADES: H.C., J.F.W. PROCARDIS controls: M. Farrall, A. Hamsten, J.F.P., H.W. PROSPER/PHASE: B.B., J.W.J., D. Stott RSI/RSII/RSIII: A. Hofman, C.M.v.D., J.C.M.W. SardiNIA: G.R.A., M.U. SHIP: M.D., H.K.K., R.R., U.V., H.V. SUVIMAX: P. Galan, S. Hercberg, P.M. TwinsUK: T.D.S. WGHS: P.M.R. YFS: M.K., T.L., O.T.R., J.V. Phenotype data acquisition and quality control: AGES: T.A., V.G., T.B.H., L.L. ARIC: A.C., S.K.G., A.C.M., D.C.R. ASPS: M. Loitfelder, R.S. BLSA: S.S.N. B58C-T1DGC: D.P.S. B58C-WTCCC: D.P.S. BHS: J.P.B., J.H. C4D Consortium: R. Clarke, J.C.H. CHS: B.M.P. CoLaus: M. Bochud, V.M., P. Vollenweider CROATIA-Korcula: C.H., O.P. CROATIA-Split: M. Boban, I.R. DGI controls: L.G., C.N.-C. EGCUT: H.A., A.K., A.M., M.-L.T. EPIC: N.J.W. Fenland: N.J.W. FHS: S.-J.H., M.G.L., D.L., R.S.V., T.J.W. FUSION: J.T. INGI CARL: A.F., F.F., P. Gasparini, S.U. INGI FVG: A.F., F.F., P. Gasparini, S.U. INGI-Val Borbera: C. Masciullo, C.S., D.T. INCHIANTI: A.M.C. KORA S3: C.G. KORA F4: A.D. LifeLines: M.M.v.d.K. LOLIPOP: J.C.C., J.S.K., J.S. LBC1921/LBC1936: I.J.D., L.M.L., J.M.S. MICROS: M. Facheris, A. Pfeufer MESA: G.L.B., X.G., W.P. MIGen controls: G.L., O.M., C.J.O., V.S., D. Siscovick NESDA: X. Lu, I.M.N., B.W.P., H. Snieder NEURO-CHARGE Consortium: M. Breteler, S.D., A.L.D., M. Fornage NFBC1966: P.E., M.-R.J., J. Laitinen, A. Pouta, P.Z. NSPHS: U.B.G. NTR: D.I.B., E.J.C.d.G., G. Willemsen ORCADES: S.H.W., J.F.W. PROCARDIS controls: J.F.P. PROSPER/PHASE: D. Stott, S.T. RSI/RSII/RSIII: F.U.S.M.-R., E.J.G.S., C.M.v.D., G.C.V., J.C.M.W. SardiNIA: M.O., M.U. SHIP: M.D., R.R., H.V. SUVIMAX: P. Galan, M. Lathrop TwinsUK: T.D.S. WGHS: P.M.R. YFS: M.K., T.L., O.T.R., J.V. Genotype data acquisition and quality control: AGES: A.V.S. ARIC: A.C., G.B.E., S.K.G., A.C.M., D.C.R., G.S. ASPS: P. Gider, H. Schmidt, M.Z. BLSA: D. Hernandez B58C-T1DGC: S. Heath, W.L.M. B58C-WTCCC: W.L.M. BHS: J.P.B., R.J.W. C4D Consortium: J.C.H., H.O. CHS: J.C.B., N.L.G., K.D.T. CoLaus: V.M., P. Vollenweider CROATIA-Korcula: C.H., O.P. CROATIA-Split: I.R. CROATIA-Vis: V.V. DGI controls: D.A., B.F.V. EGCUT: T.E., T.H. EPIC: N.J.W. Fenland: R.J.F.L., J. Luan, N.J.W. FHS: S.-J.H., M.G.L. FUSION: F.S.C. INGI CARL: A.P.d'A. INGI FVG: A.P.d'A. INGI Val Borbera: C. Masciullo, C.S., D.T. INCHIANTI: A.S. KORA S3: C.G., M. Laan, E.O. KORA F4: T.M., H.-E.W. LifeLines: B.Z.A. LOLIPOP: J.C.C., J.S.K., J.S., W.Z. LBC1921/LBC1936: G.D., I.J.D. MICROS: I.P. MESA: G.L.B., Y.-D.I.C., X.G. MIGen controls: G.L., O.M., C.J.O., V.S., D.S. NESDA: J.F., X. Lu, I.M.N., B.W.P., H. Snieder NFBC1966: P.E., M.-R.J., J. Laitinen, P.Z. NTR: D.I.B., E.J.C.d.G., J.-J.H., G. Willemsen ORCADES: H.C., J.F.W. PROCARDIS controls: A.G., J.F.P. PROSPER/PHASE: S.T. RSI/RSII/RSIII: F.R., A.G.U. SardiNIA: G.R.A. SHIP: H.K.K., U.V., H.V. SUVIMAX: S. Heath, M. Lathrop TwinsUK: M.M., S.-Y.S., N.S., F.Z. WGHS: D.I.C., A.N.P. YFS: T.L., O.T.R. Data analysis: AGES: T.A., A.V.S. ARIC: A.C., G.B.E., A.C.M., V.P., D.C.R., G.S. ASPS: P. Gider, H. Schmidt, M.Z. BLSA: T.T. B58C-T1DGC: D.P.S. B58C-WTCCC: D. Hadley, D.P.S. BHS: A.W.M., L.J.P., R.J.W. C4D Consortium: J.C.H., H.O., CHS: J.C.B., N.L.G., K.M.R. CoLaus: J.S.B., S. Bergmann, M. Bochud, T.J. CROATIA-Korcula: C.H., O.P. CROATIA-Split: C.H. CROATIA-Vis: V.V. DGI controls: P.A., C.N.-C., B.F.V. EchoGen Consortium: J.F.F. EGCUT: T.E., T.H. ENGAGE: M.P. EPIC: I.B., R.J.F.L., N.J.W., J.H.Z. ERF: A.C.J.W.J., Y.A. Fenland: R.J.F.L., J. Luan FHS: S.-J.H., M.G.L. FUSION: A.U.J. INGI CARL: N.P. INGI FVG: N.P. INGI Val Borbera: T.C., G.P., C.S., D.T. KORA S3: S.E., S.S. KORA F4: B.K. LifeLines: B.Z.A. LOLIPOP: J.C.C., J.S.K., X. Li, J.S., W.Z. LBC1921/LBC1936: L.M.L. MICROS: F.D.G.M. MESA: Y-D.I.C., X.G., W.P. MIGen controls: G.L. NESDA: J.F., X. Lu NEURO-CHARGE Consortium: S.D., A.L.D., M. Fornage NFBC1966: P.F.O. NSPHS:W.I. NTR: J.-J.H. ORCADES: P.N., S.H.W., J.F.W. PROCARDIS controls: M. Farrall, A.G., J.F.P. PROSPER/PHASE: J.W.J., S.T. RSI/RSII/RSIII: N.A., S.K., C.M.v.D., G.C.V. SardiNIA: J.L.B.-G. SHIP: U.V. SUVIMAX: T.J., P.M. TwinsUK: N.S., F.Z. WGHS: D.I.C., L.M.R., YFS: T.L., O.T.R.

Competing interests

A.C. is managed by Johns Hopkins Medicine. I.B. and spouse own stock in Incyte Ltd and GlaxoSmithKline. A.N.P. is an employee of Amgen. G.F.M. is owner of Cardiovascular Engineering, Inc, a company that designs and manufactures devices that measure vascular stiffness. The company uses these devices in clinical studies that evaluate the effects of diseases and interventions on vascular stiffness. V.M. is an employee of GlaxoSmithKline plc. A. Plump is an employee of Merck and Co, Inc.

Corresponding authors

Correspondence to Martin D Tobin or Paul Elliott or Cornelia M van Duijn.

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    Supplementary Text and Figures

    Supplementary Figures 1–4, Supplementary Tables 1–3 and Supplementary Note.

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DOI

https://doi.org/10.1038/ng.922

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