Article | Published:

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Nature Genetics volume 49, pages 403415 (2017) | Download Citation

  • A Corrigendum to this article was published on 27 September 2017

This article has been updated

Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure–raising genetic variants on future cardiovascular disease risk.

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Change history

  • 20 February 2017

    In the version of this article initially published online, the name of Chiara Batini was misspelled as Chiara Battini in the list of collaborators affiliated with International Consortium of Blood Pressure (ICBP) 1000G Analyses. The error has been corrected in the print, PDF and HTML versions of this article.

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Acknowledgements

H.R.W., C.P.C., M.R., M.R.B., P.B.M., M.B. and M.J.C. were funded by the National Institute for Health Research (NIHR) as part of the portfolio of translational research of the NIHR Biomedical Research Unit at Barts and The London School of Medicine and Dentistry. H.G. was funded by the NIHR Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre. M.R. was a recipient of a grant from the China Scholarship Council (2011632047). B.M. holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. J.M.M.H. was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834) and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). B.K. holds a British Heart Foundation Personal Chair (CH/13/2/30154). N.J.S. holds a chair funded by the British Heart Foundation and is an NIHR Senior Investigator. F.D. was funded by the MRC Unit at the University of Bristol (MC_UU_12013/1-9). P. Surendran was funded by the UK Medical Research Council (G0800270). C.L. and A.K. were funded by NHLBI intramural funding. C.N.-C. was funded by the National Institutes of Health (HL113933, HL124262). P.v.d.H. was funded by ZonMw grant 90.700.441, Marie Sklodowska-Curie GF (call, H2020-MSCA-IF-2014; project ID, 661395). N.V. was supported by a Marie Sklodowska-Curie GF grant (661395) and ICIN-NHI. N.P. received funding from the UK National Institute for Health Research Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London and also from his Senior Investigator Award. P. Sever was supported by the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. S.T. was supported by the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London. P.F.O'R. received funding from the UK Medical Research Council (MR/N015746/1) and the Wellcome Trust (109863/Z/15/Z). I.K. was supported by the EU PhenoMeNal project (Horizon 2020, 654241). A.C. was funded by the National Institutes of Health (HL128782, HL086694). M.F. was supported by a Wellcome Trust core award (090532/Z/09/Z) and the BHF Centre of Research Excellence, Oxford (RE/13/1/30181). C.H. was funded by an MRC core grant for QTL in Health and Disease programme. Some of this work used the ALICE and SPECTRE High-Performance Computing Facilities at the University of Leicester. M.J.C. is a National Institute for Health Research (NIHR) senior investigator. P.E. is a National Institute for Health Research (NIHR) senior investigator and acknowledges support from the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London, and the NIHR Health Protection Research Unit in Health Impact of Environmental Hazards (HPRU-2012-10141). As director of the MRC-PHE Centre for Environment and Health, P.E. acknowledges support from the Medical Research Council and Public Health England (MR/L01341X/1). This work used the computing resources of the UK Medical Bioinformatics partnership–aggregation, integration, visualisation and analysis of large, complex data (UK MED-BIO), which is supported by the Medical Research Council (MR/L01632X/1). This research was supported by the British Heart Foundation (grant SP/13/2/30111). Project title: Large-Scale Comprehensive Genotyping of UK Biobank for Cardiometabolic Traits and Diseases: UK CardioMetabolic Consortium (UKCMC). This research has been conducted using the UK Biobank Resource under application number 236.

Author information

Author notes

    • Helen R Warren
    • , Evangelos Evangelou
    • , Claudia P Cabrera
    • , He Gao
    • , Meixia Ren
    • , Borbala Mifsud
    • , Michael R Barnes
    • , Ioanna Tzoulaki
    • , Mark J Caulfield
    •  & Paul Elliott

    These authors contributed equally to this work.

Affiliations

  1. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Helen R Warren
    • , Claudia P Cabrera
    • , Meixia Ren
    • , Borbala Mifsud
    • , Ioanna Ntalla
    • , Morris Brown
    • , Patricia B Munroe
    • , Michael R Barnes
    •  & Mark J Caulfield
  2. National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.

    • Helen R Warren
    • , Claudia P Cabrera
    • , Meixia Ren
    • , Morris Brown
    • , Patricia B Munroe
    • , Michael R Barnes
    •  & Mark J Caulfield
  3. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • Evangelos Evangelou
    • , He Gao
    • , Marie Loh
    • , Ibrahim Karaman
    • , Marcelo P Segura Lepe
    • , John C Chambers
    • , Weihua Zhang
    • , Benjamin Lehne
    • , Ioanna Tzoulaki
    • , Anne-Claire Vergnaud
    •  & Paul Elliott
  4. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.

    • Evangelos Evangelou
    •  & Ioanna Tzoulaki
  5. MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.

    • He Gao
    • , Marjo-Riitta Jarvelin
    • , Paul Elliott
    •  & Ioanna Tzoulaki
  6. Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Praveen Surendran
    • , Rajiv Chowdhury
    •  & Joanna M M Howson
  7. Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Chunyu Liu
    •  & Daniel Levy
  8. Boston University School of Public Health, Boston, Massachusetts, USA.

    • Chunyu Liu
  9. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Chunyu Liu
    • , Daniel Levy
    • , Roby Joehanes
    • , Andrew D Johnson
    •  & Marty Larson
  10. Department of Biostatistics, University of Liverpool, Liverpool, UK.

    • James P Cook
    •  & Andrew P Morris
  11. Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Aldi T Kraja
  12. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • Fotios Drenos
  13. Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.

    • Fotios Drenos
  14. Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore.

    • Marie Loh
  15. University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.

    • Niek Verweij
    • , M Abdullah Said
    •  & Pim van der Harst
  16. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Niek Verweij
    • , Tõnu Esko
    • , Christopher Newton-Cheh
    • , Cecilia M Lindgren
    •  & Sekar Kathiresan
  17. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Niek Verweij
    • , Christopher Newton-Cheh
    •  & Sekar Kathiresan
  18. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Niek Verweij
    • , Christopher Newton-Cheh
    •  & Sekar Kathiresan
  19. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

    • Jonathan Marten
    • , Caroline Hayward
    • , Jennifer E Huffman
    • , Alan F Wright
    • , Veronique Vitart
    •  & James F Wilson
  20. Bayer Pharma, Berlin, Germany.

    • Marcelo P Segura Lepe
  21. Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

    • Paul F O'Reilly
    •  & Paul O'Reilly
  22. Data Science Institute, Lancester University, Lancaster, UK.

    • Joanne Knight
  23. University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

    • Harold Snieder
    • , Ahmad Vaez
    • , Peter J van der Most
    •  & Ilja M Nolte
  24. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

    • Norihiro Kato
  25. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.

    • Jiang He
  26. Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.

    • E Shyong Tai
  27. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • E Shyong Tai
  28. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

    • David Porteous
    • , Sarah E Harris
    •  & Archie Campbell
  29. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Maris Alver
    • , Reedik Mägi
    • , Andres Metspalu
    • , Tõnu Esko
    • , Tonu Esko
    •  & Elin Org
  30. Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK.

    • Neil Poulter
  31. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Martin Farrall
  32. University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, the Netherlands.

    • Ron T Gansevoort
  33. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

    • Sandosh Padmanabhan
    •  & David J Stott
  34. Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.

    • Alice Stanton
  35. Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

    • John Connell
  36. University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, the Netherlands.

    • Stephan J L Bakker
    • , Martin H de Borst
    •  & Marc A Seelen
  37. School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.

    • Denis C Shields
  38. National Heart and Lung Institute, Imperial College London, London, UK.

    • Simon Thom
    • , Peter Sever
    •  & Jaspal S Kooner
  39. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Danish Saleheen
  40. Centre for Non-Communicable Diseases, Karachi, Pakistan.

    • Danish Saleheen
  41. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Danish Saleheen
    •  & Kay-Tee Khaw
  42. Ealing Hospital National Health Service (NHS) Trust, Southall, UK.

    • John C Chambers
  43. Imperial College Healthcare NHS Trust, London, UK.

    • John C Chambers
    •  & Jaspal S Kooner
  44. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.

    • John C Chambers
  45. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

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

    • Daniel I Chasman
    •  & Paul M Ridker
  47. Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Aravinda Chakravarti
    • , Georg B Ehret
    • , Dan E Arking
    •  & Priyanka Nandakumar
  48. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Cecilia M Lindgren
    • , Anubha Mahajan
    • , Anuj Goel
    • , Martin Farrall
    • , Teresa Ferreira
    • , Cecila M Lindgren
    • , Hugh Watkins
    •  & Andrew P Morris
  49. Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.

    • Cecilia M Lindgren
  50. Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.

    • Jaspal S Kooner
    • , Weihua Zhang
    •  & John C Chambers
  51. National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London, London, UK.

    • Jaspal S Kooner
  52. Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

    • Bernard Keavney
    • , Maciej Tomaszewski
    •  & Bernard D Keavney
  53. Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

    • Bernard Keavney
    •  & Maciej Tomaszewski
  54. Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
    • , Christopher P Nelson
    •  & Peter S Braund
  55. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
    • , Christopher P Nelson
    •  & Peter S Braund
  56. Department of Health Sciences, University of Leicester, Leicester, UK.

    • Martin D Tobin
    • , Louise V Wain
    • , A Mesut Erzurumluoglu
    • , Nick Shrine
    • , Chiara Batini
    •  & Tineka Blake
  57. Cardiology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.

    • Georg B Ehret
    • , Li Lin
    •  & François Mach
  58. Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

    • Ahmad Vaez
  59. Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.

    • Rick Jansen
  60. Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts, USA.

    • Roby Joehanes
  61. Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.

    • Germaine C Verwoert
    • , Albert Hofman
    • , André G Uitterlinden
    •  & Oscar H Franco
  62. Department of Biological Psychology, Vrije Universiteit, Amsterdam, EMGO+ institute, VU University Medical Center, Amsterdam, the Netherlands.

    • Jouke-Jan Hottenga
    • , Eco J de Geus
    • , Gonneke Willemsen
    •  & Dorret I Boomsma
  63. Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

    • Rona J Strawbridge
    • , Mattias Frånberg
    •  & Anders Hamsten
  64. Centre for Molecular Medicine, Karolinska Universitetsjukhuset, Solna, Sweden.

    • Rona J Strawbridge
    • , Mattias Frånberg
    •  & Anders Hamsten
  65. Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA.

    • Tonu Esko
  66. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Tonu Esko
    • , Cecila M Lindgren
    •  & Christopher Newton-Cheh
  67. Population Science Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Shih-Jen Hwang
  68. Framingham Heart Study, Framingham, Massachusetts, USA.

    • Shih-Jen Hwang
    •  & Daniel Levy
  69. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.

    • Xiuqing Guo
    • , Jerome I Rotter
    •  & Jie Yao
  70. Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.

    • Zoltan Kutalik
    •  & Murielle Bochud
  71. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Zoltan Kutalik
  72. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.

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

    • Stella Trompet
  74. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

    • Alexander Teumer
  75. DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.

    • Alexander Teumer
    • , Marcus Dörr
    •  & Uwe Völker
  76. Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany.

    • Janina S Ried
    •  & Annette Peters
  77. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    •  & Bruce M Psaty
  78. Icelandic Heart Association, Kopavogur, Iceland.

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

    • Albert V Smith
    •  & Vilmundur Gudnason
  80. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.

    • Najaf Amin
    • , Ben A Oostra
    •  & Cornelia M van Duijn
  81. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.

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

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  83. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.

    • Nicholas J Wareham
    • , Jian'an Luan
    • , Claudia Langenberg
    • , Robert A Scott
    •  & Jing Hua Zhao
  84. Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Graz, Austria.

    • Edith Hofer
    • , Reinhold Schmidt
    •  & Ruth J F Loos
  85. Institute of Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria.

    • Edith Hofer
  86. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

    • Peter K Joshi
    • , Harry Campbell
    • , Igor Rudan
    • , Sarah Wild
    • , Markus Perola
    •  & James F Wilson
  87. Department of Health, National Institute for Health and Welfare (THL), Helsinki, Finland.

    • Kati Kristiansson
    • , Aki S Havulinna
    • , Teemu Niiranen
    • , Pekka Jousilahti
    • , Antti Jula
    • , Seppo Koskinen
    • , Paul Knekt
    •  & Veikko Salomaa
  88. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.

    • Michela Traglia
    • , Caterina M Barbieri
    • , Cinzia F Sala
    •  & Daniela Toniolo
  89. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

    • Anuj Goel
    • , Martin Farrall
    •  & Hugh Watkins
  90. Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA.

    • Mike A Nalls
  91. Kelly Services, Rockville, Maryland, USA.

    • Mike A Nalls
  92. Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Siim Sõber
    •  & Maris Laan
  93. Experimental Genetics Division, Sidra Medical and Research Center, Doha, Qatar.

    • Dragana Vuckovic
    • , Giorgia Girotto
    •  & Paolo Gasparini
  94. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.

    • Dragana Vuckovic
    • , Ilaria Gandin
    • , Marco Brumat
    • , Massimiliano Cocca
    • , Anna Morgan
    • , Giorgia Girotto
    •  & Paolo Gasparini
  95. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated institute of the University of Lübeck).

    • Fabiola Del Greco M
    • , Peter P Pramstaller
    • , Aude Saint Pierre
    •  & Andrew A Hicks
  96. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Kristin L Ayers
  97. Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain.

    • Jaume Marrugat
    •  & Roberto Elosua
  98. Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Naples, Italy.

    • Daniela Ruggiero
    • , Teresa Nutile
    • , Rossella Sorice
    •  & Marina Ciullo
  99. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.

    • Lorna M Lopez
    • , Sarah E Harris
    • , Gail Davies
    • , Alan J Gow
    • , David C M Liewald
    • , John M Starr
    •  & Ian J Deary
  100. Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.

    • Lorna M Lopez
  101. University College Dublin, UCD Conway Institute, Centre for Proteome Research, UCD, Belfield, Dublin, Ireland.

    • Lorna M Lopez
  102. Department of Immunology, Genetics and Pathology, Uppsala Universitet, Science for Life Laboratory, Uppsala, Sweden.

    • Stefan Enroth
    • , Åsa Johansson
    •  & Ulf Gyllensten
  103. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.

    • Anne U Jackson
    •  & Michael Boehnke
  104. Department of Biology, Faculty of Medicine, University of Split, Split, Croatia.

    • Tatijana Zemonik
  105. Charles Bronfman Institute for Personalized Medicine, Icachn School of Medicine at Mount Sinai, New York, New York, USA.

    • Yingchang Lu
    • , Erwin P Bottinger
    •  & Ruth J F Loos
  106. Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.

    • Nabi Shah
    • , Alex S F Doney
    •  & Colin N A Palmer
  107. Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan.

    • Nabi Shah
  108. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

    • Massimo Mangino
    • , Cristina Menni
    •  & Tim D Spector
  109. National Institute for Health Research Biomedical Research Centre, London, UK.

    • Massimo Mangino
  110. Department of Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK.

    • Bram P Prins
    •  & Eleftheria Zeggini
  111. Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.

    • Archie Campbell
    • , Sandosh Padmanabhan
    •  & Caroline Hayward
  112. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

    • Ruifang Li-Gao
    • , Renée de Mutsert
    •  & Dennis O Mook-Kanamori
  113. INSERM U1219, Bordeaux Population Health Center, Bordeaux, France.

    • Ganesh Chauhan
    • , Christophe Tzourio
    •  & Stéphanie Debette
  114. Bordeaux University, Bordeaux, France.

    • Ganesh Chauhan
    • , Christophe Tzourio
    •  & Stéphanie Debette
  115. Hunter Medical Research Institute, New Lambton, New South Wales, Australia.

    • Christopher Oldmeadow
    • , Elizabeth G Holliday
    • , Rodney Scott
    •  & Attia John
  116. Center for Statistical Genetics, Department of Biostatistics, SPH II, Ann Arbor, Michigan, USA.

    • Gonçalo Abecasis
  117. Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.

    • Maryam Abedi
  118. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Francis Collins
  119. Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK.

    • Heather J Cordell
  120. Department of Pathology, Amsterdam Medical Center, Amsterdam, the Netherlands.

    • Jeffrey J Damman
  121. Department of Psychology, University of Edinburgh, Edinburgh, UK.

    • Gail Davies
    • , David C M Liewald
    • , Alison Pattie
    •  & Ian J Deary
  122. Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

    • Joris Deelen
  123. Center for Information Technology, US National Institutes of Health, Bethesda, Maryland, USA.

    • Yusuf Demirkale
    • , Peter J Munson
    •  & Quang Tri Nguyen
  124. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.

    • Marcus Dörr
  125. Department of Numerical Analysis and Computer Science, Stockholm University, Stockholm, Sweden.

    • Mattias Frånberg
  126. Department of Public Health and Caring Sciences, Geriatrics, Uppsala, Sweden.

    • Vilmantas Giedraitis
  127. Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany.

    • Christian Gieger
  128. Department of Psychology, School of Life Sciences, Heriot-Watt University, Edinburgh, UK.

    • Alan J Gow
  129. Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA.

    • Tamara B Harris
    •  & Lenore J Launer
  130. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

    • Albert Hofman
  131. Center For Life-Course Health Research, University of Oulu, Oulu, Finland.

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

    • Marjo-Riitta Jarvelin
  133. Unit of Primary Care, Oulu University Hospital, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  134. National Heart, Lung, and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, Bethesda, Maryland, USA.

    • Andrew D Johnson
  135. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.

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

    • Mika Kähönen
  137. Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.

    • Ivana Kolcic
    •  & Ozren Polasek
  138. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.

    • Lars Lind
    •  & Johan Sundström
  139. Institute of Health and Society, Newcastle University, Newcastle-upon-Tyne, UK.

    • Chrysovalanto Mamasoula
  140. Department of Psychiatry, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.

    • Yuri Milaneschi
    •  & Brenda W J H Penninx
  141. School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Edinburgh, UK.

    • Andrew D Morris
  142. 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
  143. University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation (IPCE), Groningen, the Netherlands.

    • Albertine J Oldehinkel
    • , Harriëtte Riese
    •  & Catharina A Hartman
  144. British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

    • Sandosh Padmanabhan
  145. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Aarno Palotie
    • , Samuli Ripatti
    • , Antti-Pekka Sarin
    •  & Markus Perola
  146. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

    • Guillaume Paré
    •  & Sébastien Thériault
  147. Department of Neurology, General Central Hospital, Bolzano, Italy.

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

    • Peter P Pramstaller
  149. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

    • Olli T Raitakari
  150. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

    • Olli T Raitakari
  151. Department of Cardiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.

    • Meixia Ren
  152. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Kenneth Rice
  153. Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.

    • Antonietta Robino
  154. Institute for Translational Genomics and Population Sciences, Department of Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA.

    • Jerome I Rotter
  155. Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.

    • Yasaman Saba
    •  & Helena Schmidt
  156. INSERM U1078, Etablissement Français du Sang, Brest, France.

    • Aude Saint Pierre
  157. Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia.

    • Rodney Scott
    •  & Attia John
  158. School of Biomedical Sciences and Pharmacy, John Hunter Hospital, New Lambton, New South Wales, Australia.

    • Rodney Scott
    •  & Attia John
  159. New York Academy of Medicine, New York, New York, USA.

    • David Siscovick
  160. IRCCS Neuromed, Pozzilli, Italy.

    • Rossella Sorice
    •  & Marina Ciullo
  161. University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.

    • Morris Swertz
  162. Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

    • Kent D Taylor
  163. Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.

    • Kent D Taylor
  164. International Centre for Circulatory Health, Imperial College London, London, UK.

    • Simon Thom
  165. Department of Public Health, Bordeaux University Hospital, Bordeaux, France.

    • Christophe Tzourio
  166. Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.

    • André G Uitterlinden
  167. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.

    • Uwe Völker
  168. Department of Internal Medicine, Lausanne University Hospital, CHUV, Lausanne, Switzerland.

    • Peter Vollenweider
  169. Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

    • David Conen
  170. Department of Neurology, Bordeaux University Hospital, Bordeaux, France.

    • Stéphanie Debette
  171. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.

    • Dennis O Mook-Kanamori
  172. Mindich Child Health Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Ruth J F Loos
  173. Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.

    • John M Starr
  174. Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.

    • Jaakko Tuomilehto
  175. South Ostrobothnia Central Hospital, Seinäjoki, Finland.

    • Jaakko Tuomilehto
  176. Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.

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

    • Jaakko Tuomilehto
  178. Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.

    • Maris Laan
  179. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, USA.

    • YongMei Liu
  180. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Markus Perola
  181. Department of Neurology, Medical University Graz, Graz, Austria.

    • Helena Schmidt
  182. Department of Epidemiology University of Washington, Seattle, Washington, USA.

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

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

    • Bruce M Psaty
  185. Institute of Physiology, University Medicine Greifswald, Karlsburg, Germany.

    • Rainer Rettig
  186. Department of Pulmonary Physiology and Sleep, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

    • Alan James
  187. School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.

    • Alan James
  188. Population Health Research Institute, St George's, University of London, London, UK.

    • David P Strachan
  189. Department of Medicine, Columbia University Medical Center, New York, New York, USA.

    • Walter Palmas
  190. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

    • Erik Ingelsson
  191. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

    • Erik Ingelsson

Consortia

  1. The International Consortium of Blood Pressure (ICBP) 1000G Analyses

    BIOS Consortium

    Lifelines Cohort Study

    Understanding Society Scientific group

  2. The CHD Exome+ Consortium

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

  3. The ExomeBP Consortium

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

  4. The T2D-GENES Consortium

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

  5. The GoT2DGenes Consortium

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

  6. The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium

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

  7. The International Genomics of Blood Pressure (iGEN-BP) Consortium

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

  8. The UK Biobank CardioMetabolic Consortium BP working group

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

Authors

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Contributions

Central analysis: H.R.W., C.P.C., H.G., M.R.B., M.P.S.L., M.R., I.T., B.M., I.K., E.E. Writing of the manuscript: H.R.W., M.R.B., E.E., C.P.C., H.G., I.T., B.M., M.R., M.J.C., P.E. (with group leads, M.J.C., P.E.). Working group membership: M.J.C., H.R.W., E.E., I.T., P.B.M., L.V.W., N.J.S., M.T., J.M.M.H., M.D.T., I.N., B.K., H.G., M.R.B., C.P.C., J.S.K., P.E. (with co-chairs M.J.C., P.E.). Replication consortium contributor: (ICBP-1000G) G.B.E., L.V.W., D.L., A.C., M.J.C., M.D.T., P.F.O'R., J.K., H.S.; (CHD Exome+ Consortium) P. Surendran, R.C., D.S., J.M.M.H.; (ExomeBP Consortium) J.P.C., F.D., P.B.M.; (T2D-GENES Consortium and GoT2DGenes Consortium) C.M.L.; (CHARGE) G.B.E., C.L., A.T.K., D.L., C.N.-C., D.I.C.; (iGEN-BP) M.L., J.C.C., N.K., J.H., E.S.T., P.E., J.S.K., P.v.d.H. Replication study contributor: (Lifelines) N.V., P.v.d.H., H.S., M.A.S.; (GS:SFHS) J.M., C.H., D.P., S.P.; (EGCUT) T.E., M.A., R.M., A.M.; (PREVEND) P.v.d.H., N.V., R.T.G., S.J.L.B.; (ASCOT) H.R.W., M.J.C., P.B.M., P.S., N.P., A.S., D.S., S.T.; (BRIGHT) H.R.W., M.J.C., P.B.M., M.B., M.F., J.C.; (Airwave) H.G., E.E., M.P.S.L., I.K., I.T., P.E. All authors critically reviewed and approved the final version of the manuscript.

Competing interests

M.J.C. is Chief Scientist for Genomics England, a wholly owned UK government company. He leads the 100,000 Genomes Project, which includes syndromic forms of blood pressure.

Corresponding authors

Correspondence to Mark J Caulfield or Paul Elliott.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–16 and Supplementary Note

Excel files

  1. 1.

    Supplementary Tables 1–31

    Supplementary Tables 1–31

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng.3768

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