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

Nature Genetics volume 48, pages 1171–1184 (2016)Cite this article

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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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Figure 1: Manhattan plots for SBP and DBP from the stage 4 Cardio-MetaboChip-wide meta-analysis.
Figure 2: Enrichment of DNase I–hypersensitive sites among blood pressure loci in 123 different cell types.

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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

  1. Andrew P Morris: A list of members and affiliations appears in the Supplementary Note.

  2. Georg B Ehret and Teresa Ferreira: These authors contributed equally to this work.

  3. Andrew P Morris, Christopher Newton-Cheh and Patricia B Munroe: These authors jointly directed this work.

Authors and 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. Department of Medicine, Cardiology, 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. Department of Medicine, Cardiovascular Research Unit, Center for Molecular 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. Department of Epidemiology and Public Health, Genetic Epidemiology Group, 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. Los Angeles Biomedical Research Institute and Department of Pediatrics at Harbor-UCLA Medical Center, Institute for Translational Genomics and Population Sciences, 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. Department of Epidemiology, Genetic Epidemiology Unit, 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. Department of Medicine, Cardiovascular Health Research Unit, 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. Department of Public Health and Primary Care, NIHR Blood and Transplant Research Unit in Donor Health and Genomics, 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

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  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. Department of Molecular Medicine and Surgery, Cardiothoracic Surgery Unit, 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. Department of Clinical and Experimental Medicine, Epidemiology and Preventive Medicine (EPIMED) Research Centre, 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. Department of Public Health and General Practice, HUNT Research Centre, 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. Department of Medicine, Section of Computational Biomedicine, 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. Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, 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. Department of Medicine, Section of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts, USA

    Ramachandran S Vasan

  234. Department of Medicine, Cardiology, 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

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Consortia

CHARGE-EchoGen Consortium

CHARGE-HF Consortium

Wellcome Trust Case Control Consortium

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.

Corresponding authors

Correspondence to Christopher Newton-Cheh or Patricia B Munroe.

Ethics declarations

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.

Additional information

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

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

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

Supplementary information

Supplementary Text and Figures

Supplementary Note and Supplementary Figures 1–10. (PDF 22466 kb)

Supplementary Table 1

Individual cohort study information and blood pressure measurement methods. (XLSX 22 kb)

Supplementary Table 2

Genotyping methods. (XLSX 23 kb)

Supplementary Table 3

Data type contribution and participant characteristics. (XLSX 26 kb)

Supplementary Table 4

Meta-analysis stage 4 results. (XLSX 12 kb)

Supplementary Table 5

UK-CardioMetabolic Consortium validation. (XLSX 12 kb)

Supplementary Table 6

Loci identified by GCTA with multiple signals of association. (XLSX 18 kb)

Supplementary Table 7

All SNPs selected by GCTA as independently associated with SBP. (XLSX 29 kb)

Supplementary Table 8

All SNPs selected by GCTA as independently associated with DBP. (XLSX 31 kb)

Supplementary Table 9

List of SNPs at genome-wide significant Cardio-MetaboChip loci for secondary analyses. (XLSX 17 kb)

Supplementary Table 10

Conditional analysis using the WGHS data set. (XLSX 29 kb)

Supplementary Table 11

Summary of Cardio-MetaboChip blood pressure fine-mapping regions. (XLSX 11 kb)

Supplementary Table 12

Ninety-nine percent credible intervals at Cardio-MetaboChip blood pressure fine-mapping regions. (XLSX 17 kb)

Supplementary Table 13

Ninety-nine percent credible causal SNPs at Cardio-MetaboChip blood pressure fine-mapping regions. (XLSX 59 kb)

Supplementary Table 14

eSNP analysis for cell types other than whole blood. (XLSX 15 kb)

Supplementary Table 15

eSNP analysis for whole blood. (XLSX 21 kb)

Supplementary Table 16

Analysis of enrichment of DNase-hypersensitive sites among the blood pressure loci, by cell type. (XLSX 59 kb)

Supplementary Table 17

Tissue categorization for DNase-hypersensitive site analyses. (XLSX 19 kb)

Supplementary Table 18

Analysis of enrichment of DNase-hypersensitive sites among the blood pressure loci, grouping cell types by tissue. (XLSX 13 kb)

Supplementary Table 19

Analysis of enrichment of methylation sites among the blood pressure loci. (XLSX 10 kb)

Supplementary Table 20

Blood pressure SNPs enriched in DHS sites in blood vessels. (XLSX 15 kb)

Supplementary Table 21

MAGENTA analysis. (XLSX 10 kb)

Supplementary Table 22

DEPICT analysis. (XLSX 9 kb)

Supplementary Table 23

FAIRE analysis. (XLSX 14 kb)

Supplementary Table 24

Non-European meta-analysis. (XLSX 74 kb)

Supplementary Table 25

Detailed results of risk score analyses for each SNP. (XLSX 72 kb)

Supplementary Table 26

Genetic blood pressure risk score analysis applied to related cardiovascular phenotypes. (XLSX 9 kb)

Supplementary Table 27

Genes at new blood pressure loci using DEPICT. (XLSX 11 kb)

Supplementary Data

Cardio-MetaboChip blood pressure association statistics (P values). Full results can be obtained via dbGaP. (CSV 8329 kb)

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Ehret, G., Ferreira, T., Chasman, D. et al. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nat Genet 48, 1171–1184 (2016). https://doi.org/10.1038/ng.3667

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