Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Praveen Surendran; Fotios Drenos; Robin Young; Helen Warren; James P. Cook; Alisa K. Manning; Niels Grarup; Xueling Sim; Daniel R. Barnes; Kate Witkowska; James R. Staley; Vinicius Tragante; Taru Tukiainen; Hanieh Yaghootkar; Nicholas Masca; Daniel F. Freitag; Teresa Ferreira; Olga Giannakopoulou; Andrew Tinker; Magdalena Harakalova; Evelin Mihailov; Chunyu Liu; Aldi T. Kraja; Sune Fallgaard Nielsen; Asif Rasheed; Maria Samue; Wei Zhao; Lori L. Bonnycastle; Anne U. Jackson; Narisu Narisu; Amy J. Swift; Lorraine Southam; Jonathan Marten; Jeroen R. Huyghe; Alena Stancakova; Cristiano Fava; Therese Ohlsson; Angela Matchan; Kathleen E. Stirrups; Jette Bork-Jensen; Anette P. Gjesing; Jukka Kontto; Markus Perola; Susan Shaw-Hawkins; Aki S. Havulinna; He Zhang; Louise A. Donnelly; Christopher J. Groves; N. William Rayner; Matt J. Neville; Neil R. Robertson; Andrianos M. Yiorkas; Karl-Heinz Herzig; Eero Kajantie; Weihua Zhang; Sara M. Willems; Lars Lannfelt; Giovanni Malerba; Nicole Soranzo; Elisabetta Trabetti; Niek Verweij; Evangelos Evangelou; Alireza Moayyeri; Anne-Claire Vergnaud; Christopher P. Nelson; Alaitz Poveda; Tibor V. Varga; Muriel Caslake; Anton J. M. de Craen; Stella Trompet; Jian'an Luan; Robert A. Scott; Sarah E. Harris; David C. M. Liewald; Riccardo Marioni; Cristina Menni; Aliki-Eleni Farmaki; Goran Hallmans; Frida Renstrom; Jennifer E. Huffman; Maija Hassinen; Stephen Burgess; Ramachandran S. Vasan; Janine F. Felix; Maria Uria-Nickelsen; Anders Malarstign; Dermot F. Reilly; Maarten Hoek; Thomas F. Vogt; Honghuang Lin; Wolfgang Lieb; Matthew Traylor; Hugh S. Markus; Heather M. Highland; Anne E. Justice; Eirini Marouli; Jaana Lindstrom; Matti Uusitupa; Pirjo Komulainen; Timo A. Lakka; Rainer Rauramaa; Ozren Polasek; Igor Rudan; Olov Rolandsson; Paul W. Franks; George Dedoussis; Timothy D. Spector; Pekka Jousilahti; Satu Mannisto; Ian J. Deary; John M. Starr; Claudia Langenberg; Nick J. Wareham; Morris J. Brown; Anna F. Dominiczak; John M. Connell; J. Wouter Jukema; Naveed Sattar; Ian Ford; Chris J. Packard; Tonu Esko; Reedik Magi; Andres Metspalu; Rudolf A. de Boer; Peter van der Meer; Pim van der Harst; Giovanni Gambaro; Erik Ingelsson; Lars Lind; Paul I. W. de Bakker; Mattijs E. Numans; Ivan Brandslund; Cramer Christensen; Eva R. B. Petersen; Eeva Korpi-Hyovalti; Heikki Oksa; John C. Chambers; Jaspal S. Kooner; Alexandra I. F. Blakemore; Steve Franks; Marjo-Riitta Jarvelin; Lise L. Husemoen; Allan Linneberg; Tea Skaaby; Betina Thuesen; Fredrik Karpe; Jaakko Tuomilehto; Alex S. F. Doney; Andrew D. Morris; Colin N. A. Palmer; Oddgeir Lingaas Holmen; Kristian Hveem; Cristen J. Willer; Tiinamaija Tuomi; Leif Groop; AnneMari Karajamaki; Aarno Palotie; Samuli Ripatti; Veikko Salomaa; Dewan S. Alam; Abdulla Al Shafi Majmnder; Emanuele Di Angelantonio; Rajiv Chowdhury; Mark I. McCarthy; Neil Poulter; Alice V. Stanton; Peter Sever; Philippe Amouyel; Dominique Arveiler; Stefan Blankenberg; Jean Ferrieres; Frank Kee; Kari Kuulasmaa; Martina Muller-Nurasyid; Giovanni Veronesi; Jarmo Virtamo; Panos Deloukas; Paul Elliott; Eleftheria Zeggini; Sekar Kathiresan; Olle Melander; Johanna Kuusisto; Markku Laakso; Sandosh Padmanabhan; David J. Porteous; Caroline Hayward; Generation Scotland; Francis S. Collins; Karen L. Mohlke; Torben Hansen; Oluf Pedersen; Michael Boehnke; Heather M. Stringham; Philippe Frossard; Christopher Newton-Cheh; Martin D. Tobin; Borge Gronne Nordestgaard; Mark J. Caulfield; Anubha Mahajan; Andrew P. Morris; Maciej Tomaszewski; Nilesh J. Samani; Danish Saleheen; Folkert W. Asselbergs; Cecilia M. Lindgren; John Danesh; Louise V. Wain; Adam S. Butterworth; Joanna M. M. Howson; Patricia B. Munroe; Understanding Soc Sci Grp

doi:10.1038/ng.3654

Back

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Journal article

Peer reviewed

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Praveen Surendran, Fotios Drenos, Robin Young, Helen Warren, James P. Cook, Alisa K. Manning, Niels Grarup, Xueling Sim, Daniel R. Barnes, Kate Witkowska, …

Nature genetics, Vol.48(10), pp.1151-1161

01/10/2016

DOI: https://doi.org/10.1038/ng.3654

PMCID: PMC5056636

PMID: 27618447

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

Metrics

1 Record Views

See more details

Details

Title: Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
Creators - without role: Praveen Surendran - University of Cambridge
Fotios Drenos - University of Bristol
Robin Young - University of Cambridge
Helen Warren - Queen Mary University of London
James P. Cook - University of Leicester
Alisa K. Manning - Supreme Council Of Health
Niels Grarup - University of Copenhagen
Xueling Sim - Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
Daniel R. Barnes - University of Cambridge
Kate Witkowska - Queen Mary University of London
James R. Staley - University of Cambridge
Vinicius Tragante - College Station Medical Center
Taru Tukiainen - Supreme Council Of Health
Hanieh Yaghootkar - University of Exeter
Nicholas Masca - University of Leicester
Daniel F. Freitag - University of Cambridge
Teresa Ferreira - University of Oxford
Olga Giannakopoulou - Queen Mary University of London
Andrew Tinker - Queen Mary University of London
Magdalena Harakalova - College Station Medical Center
Evelin Mihailov - University of Tartu
Chunyu Liu - NHLBI, Framingham, MA USA
Aldi T. Kraja - Supreme Council Of Health
Sune Fallgaard Nielsen - Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark
Asif Rasheed - Ctr Noncommunicable Dis, Karachi, Pakistan
Maria Samue - Ctr Noncommunicable Dis, Karachi, Pakistan
Wei Zhao - Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA
Lori L. Bonnycastle - College Station Medical Center
Anne U. Jackson - Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
Narisu Narisu - College Station Medical Center
Amy J. Swift - College Station Medical Center
Lorraine Southam - University of Oxford
Jonathan Marten - University of Edinburgh
Jeroen R. Huyghe - Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
Alena Stancakova - University of Eastern Finland
Cristiano Fava - Lund University
Therese Ohlsson - Lund University
Angela Matchan - Wellcome Sanger Institute
Kathleen E. Stirrups - Queen Mary University of London
Jette Bork-Jensen - University of Copenhagen
Anette P. Gjesing - University of Copenhagen
Jukka Kontto - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Markus Perola - University of Tartu
Susan Shaw-Hawkins - Queen Mary University of London
Aki S. Havulinna - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
He Zhang - College Station Medical Center
Louise A. Donnelly - University of Dundee
Christopher J. Groves - University of Oxford
N. William Rayner - University of Oxford
Matt J. Neville - University of Oxford
Neil R. Robertson - University of Oxford
Andrianos M. Yiorkas - College Station Medical Center
Karl-Heinz Herzig - University of Oulu
Eero Kajantie - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Weihua Zhang - Supreme Council Of Health
Sara M. Willems - University of Cambridge
Lars Lannfelt - Uppsala University
Giovanni Malerba - University of Verona
Nicole Soranzo - University of Cambridge
Elisabetta Trabetti - University of Verona
Niek Verweij - Broad Institute
Evangelos Evangelou - Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England
Alireza Moayyeri - Supreme Council Of Health
Anne-Claire Vergnaud - Supreme Council Of Health
Christopher P. Nelson - University of Leicester
Alaitz Poveda - Lund University
Tibor V. Varga - Lund University
Muriel Caslake - University of Glasgow
Anton J. M. de Craen - Leiden University
Stella Trompet - Leiden University
Jian'an Luan - University of Cambridge
Robert A. Scott - University of Cambridge
Sarah E. Harris - University of Edinburgh
David C. M. Liewald - University of Edinburgh
Riccardo Marioni - University of Edinburgh
Cristina Menni - Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
Aliki-Eleni Farmaki - Harokopio University of Athens
Goran Hallmans - Umeå University
Frida Renstrom - Lund University
Jennifer E. Huffman - NHLBI, Framingham, MA USA
Maija Hassinen - College Station Medical Center
Stephen Burgess - University of Cambridge
Ramachandran S. Vasan - NHLBI, Framingham, MA USA
Janine F. Felix - Erasmus MC
Maria Uria-Nickelsen - Pfizer Worldwide Res & Dev, Dev Management & Planning, Cambridge, MA USA
Anders Malarstign - Pfizer Worldwide Res & Dev, Stockholm, Sweden
Dermot F. Reilly - Merck
Maarten Hoek - Merck Res Labs, Cardiometab Dis, Kenilworth, NJ USA
Thomas F. Vogt - Merck Res Labs, Cardiometab Dis, Kenilworth, NJ USA
Honghuang Lin - NHLBI, Framingham, MA USA
Wolfgang Lieb - Univ Kiel, Inst Epidemiol & Biobank Popgen, Kiel, Germany
Matthew Traylor - University of Cambridge
Hugh S. Markus - University of Cambridge
Heather M. Highland - Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA
Anne E. Justice - Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA
Eirini Marouli - Queen Mary University of London
Jaana Lindstrom - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Matti Uusitupa - University of Eastern Finland
Pirjo Komulainen - College Station Medical Center
Timo A. Lakka - College Station Medical Center
Rainer Rauramaa - College Station Medical Center
Ozren Polasek - University of Edinburgh
Igor Rudan - University of Edinburgh
Olov Rolandsson - Umeå University
Paul W. Franks - Lund University
George Dedoussis - Harokopio University of Athens
Timothy D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
Pekka Jousilahti - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Satu Mannisto - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Ian J. Deary - University of Edinburgh
John M. Starr - University of Edinburgh
Claudia Langenberg - University of Cambridge
Nick J. Wareham - University of Cambridge
Morris J. Brown - Queen Mary University of London
Anna F. Dominiczak - University of Glasgow
John M. Connell - University of Dundee
J. Wouter Jukema - Leiden University
Naveed Sattar - University of Glasgow
Ian Ford - University of Glasgow
Chris J. Packard - University of Glasgow
Tonu Esko - Supreme Council Of Health
Reedik Magi - University of Tartu
Andres Metspalu - University of Tartu
Rudolf A. de Boer - University of Groningen
Peter van der Meer - University of Groningen
Pim van der Harst - University of Groningen
Giovanni Gambaro - Pontifícia Universidade Católica de São Paulo
Erik Ingelsson - Uppsala University
Lars Lind - Uppsala University
Paul I. W. de Bakker - College Station Medical Center
Mattijs E. Numans - College Station Medical Center
Ivan Brandslund - Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark
Cramer Christensen - College Station Medical Center
Eva R. B. Petersen - Lillebaelt Hosp, Dept Clin Immunol & Biochem, Vejle, Denmark
Eeva Korpi-Hyovalti - College Station Medical Center
Heikki Oksa - Tampere University
John C. Chambers - Supreme Council Of Health
Jaspal S. Kooner - Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England
Alexandra I. F. Blakemore - College Station Medical Center
Steve Franks - Imperial Coll London, Inst Reprod & Dev Biol, London, England
Marjo-Riitta Jarvelin - Imperial Coll London, Dept Epidemiol & Biostat, Med Res Council Publ Hlth England Ctr Environm &, Sch Publ Hlth,Fac Med, St Marys Campus, London, England
Lise L. Husemoen - Capital University
Allan Linneberg - Capital University
Tea Skaaby - Capital University
Betina Thuesen - Capital University
Fredrik Karpe - University of Oxford
Jaakko Tuomilehto - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Alex S. F. Doney - University of Dundee
Andrew D. Morris - University of Edinburgh
Colin N. A. Palmer - University of Dundee
Oddgeir Lingaas Holmen - Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway
Kristian Hveem - Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway
Cristen J. Willer - College Station Medical Center
Tiinamaija Tuomi - Folkhalsan Res Ctr, Helsinki, Finland
Leif Groop - University of Helsinki
AnneMari Karajamaki - Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland
Aarno Palotie - Broad Institute
Samuli Ripatti - Wellcome Sanger Institute
Veikko Salomaa - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Dewan S. Alam - ICDDR, Dhaka, Bangladesh
Abdulla Al Shafi Majmnder - Natl Inst Cardiovasc Dis, Dhaka, Bangladesh
Emanuele Di Angelantonio - University of Cambridge
Rajiv Chowdhury - University of Cambridge
Mark I. McCarthy - University of Oxford
Neil Poulter - Supreme Council Of Health
Alice V. Stanton - Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland
Peter Sever - Lung Institute
Philippe Amouyel - Univ Lille, UMR 1167, Risk Factors & Mol Determinants Aging Related Dis, Lille, France
Dominique Arveiler - University of Strasbourg
Stefan Blankenberg - Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany
Jean Ferrieres - Inserm
Frank Kee - Queens University
Kari Kuulasmaa - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Martina Muller-Nurasyid - Helmholtz Zentrum München
Giovanni Veronesi - University of Insubria
Jarmo Virtamo - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Panos Deloukas - Queen Mary University of London
Paul Elliott - Imperial Coll London, Dept Epidemiol & Biostat, Med Res Council Publ Hlth England Ctr Environm &, Sch Publ Hlth,Fac Med, St Marys Campus, London, England
Eleftheria Zeggini - Wellcome Sanger Institute
Sekar Kathiresan - Broad Institute
Olle Melander - Lund University
Johanna Kuusisto - University of Eastern Finland
Markku Laakso - University of Eastern Finland
Sandosh Padmanabhan - University of Glasgow
David J. Porteous - University of Edinburgh
Caroline Hayward - University of Edinburgh
Generation Scotland - Supreme Council Of Health
Francis S. Collins - College Station Medical Center
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC USA
Torben Hansen - University of Copenhagen
Oluf Pedersen - University of Copenhagen
Michael Boehnke - Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
Heather M. Stringham - Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
Philippe Frossard - Ctr Noncommunicable Dis, Karachi, Pakistan
Christopher Newton-Cheh - Broad Institute
Martin D. Tobin - University of Leicester
Borge Gronne Nordestgaard - Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark
Mark J. Caulfield - Queen Mary University of London
Anubha Mahajan - University of Oxford
Andrew P. Morris - University of Liverpool
Maciej Tomaszewski - University of Leicester
Nilesh J. Samani - University of Leicester
Danish Saleheen - University of Cambridge
Folkert W. Asselbergs - College Station Medical Center
Cecilia M. Lindgren - Broad Institute
John Danesh - University of Cambridge
Louise V. Wain - University of Leicester
Adam S. Butterworth - University of Cambridge
Joanna M. M. Howson - University of Cambridge
Patricia B. Munroe - Queen Mary University of London
Understanding Soc Sci Grp
Publication Details: Nature genetics, Vol.48(10), pp.1151-1161
Publisher: Springer Nature
Number of pages: 11
Grant note: SP/04/002; SP/08/005/25115; SP/09/002; RG/07/005/23633; RG/15/15/31742; RG/14/5/30893; SP/10/6/28562; FS/14/66/31293; PG/02/128 / British Heart Foundation R01 MH101822; R01 MH101810; R01 MH063706; RL1 MH083268 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) Z01HG000024 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01LM010098 / NATIONAL LIBRARY OF MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) R165-2013-15410 / Lundbeck Foundation; Lundbeckfonden R01 DA006227 / NIDA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) R01HD057194 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) 068545/Z/02; 086596/Z/08/Z; 084723/Z/08/Z; WT098381; 085475; 098051; 083948; WT091310; WT098017; 100114 / Wellcome Trust; European Commission R01HL087679 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 HD057194 / NICHD NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) RG/08/014/24067 / British Heart Foundation HHSN261200800001E / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Z01 HG000024 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) NNF12OC1016374 / Novo Nordisk Fonden; Novo Nordisk Foundation R01MH101810 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) P30DK020595 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) NF-SI-0507-10267 / National Institute for Health Research; National Institute for Health Research (NIHR) R01DA006227 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission G0600705; G0902313; G0700931; G0800270; G0802782; MC_UU_12013/5; G0600237; MR/K006584/1; G0500539; G0000934; MC_PC_U127561128; G9521010D; MC_UU_12015/1; MR/K026992/1; G0601966; MR/L01341X/1; MC_U106179471; G1002319 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission CZD/16/6/4 / Chief Scientist Office R01 HL087679; R01 HL109946; R01 HL127564; R01 HL107816; HHSN268201000029C; T32 HL007055; K99 HL094535 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 LM010098 / NLM NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) MR/L003120/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission G0600705 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Biotechnology and Biological Sciences Research Council; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) P30 DK020572; U01 DK085526; R01 DK093757; R01 DK072193; U01 DK062370; U01 DK085501; P30 DK020595; RC2 DK088389; U01 DK085545; U01 DK085584; U01 DK085524 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Identifiers: 9939899908331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article