The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Georg Ehret(Johns Hopkins University), Teresa Ferreira(Centre for Human Genetics), Daniel I. Chasman(Brigham and Women's Hospital), Anne Jackson(University of Michigan), Ellen M. Schmidt(University of Michigan), Toby Johnson(Queen Mary University of London), Guðmar Þorleifsson(deCODE Genetics (Iceland)), Jian’an Luan(University of Cambridge), Louise A Donnelly(University of Dundee), Stavroula Kanoni(Queen Mary University of London), Ann-Kristin Petersen(Helmholtz Zentrum München), Vasyl Pihur(Johns Hopkins University), Rona J. Strawbridge(Karolinska University Hospital), Dmitry Shungin(Malmö University), Maria Hughes(Queen's University Belfast), Osorio Meirelles(Institute on Aging), Marika Kaakinen(Hammersmith Hospital), Nabila Bouatia‐Naji(Délégation Paris 5), Kati Kristiansson(Finnish Institute for Health and Welfare), Sonia Shah(MRC Epidemiology Unit), Marcus E. Kleber(Heidelberg University), Xiuqing Guo(UCLA Medical Center), Leo‐Pekka Lyytikäinen(Tampere University), Cristiano Fava(University of Verona), Niclas Eriksson(Uppsala University), Ilja M. Nolte(University Medical Center Groningen), Patrik K. E. Magnusson(Karolinska Institutet), Elias Salfati(Stanford University), Lοukianos S. Rallidis(National and Kapodistrian University of Athens), Elizabeth Theusch, Andrew J. Smith(University of Iceland), Lasse Folkersen(Karolinska Institutet), Kate Witkowska(Queen Mary University of London), Tune H. Pers(Statens Serum Institut), Roby Joehanes(National Heart Lung and Blood Institute), Stuart K. Kim(Stanford University), Lazaros Lataniotis(Queen Mary University of London), Rick Jansen(Amsterdam UMC Location Vrije Universiteit Amsterdam), Andrew D. Johnson(National Heart Lung and Blood Institute), Helen R. Warren(Queen Mary University of London), Young Jin Kim(Korea National Institute of Health), Wei Zhao, Ying Wu(University of North Carolina at Chapel Hill), Bamidele O. Tayo(Loyola University Chicago), Murielle Bochud(University Hospital of Lausanne), Devin Absher(HudsonAlpha Institute for Biotechnology), Linda S. Adair(University of North Carolina at Chapel Hill), Najaf Amin(Erasmus University Rotterdam), Dan E. Arking(Johns Hopkins University), Tomas Axelsson(Uppsala University), Damiano Baldassarre(University of Milan), Beverley Balkau(Inserm), Stefania Bandinelli(Azienda Sanitaria di Firenze), Michael R. Barnes(Queen Mary University of London), Inês Barroso(Wellcome Sanger Institute), Steve Bevan(University of Lincoln), Joshua C Bis(University of Washington), Gyða Björnsdóttir(deCODE Genetics (Iceland)), Michael Boehnke(University of Michigan), Eric Boerwinkle(The University of Texas Health Science Center at Houston), Lori L. Bonnycastle(National Human Genome Research Institute), Dorret I. Boomsma, Stefan R. Bornstein(University Hospital Carl Gustav Carus), Morris J. Brown(Queen Mary University of London), Michel Burnier(University Hospital of Lausanne), Claudia Cabrera(Queen Mary University of London), John C. Chambers(Imperial College Healthcare NHS Trust), I‐Shou Chang(National Health Research Institutes), Ching‐Yu Cheng(Singapore National Eye Center), Peter S. Chines(National Human Genome Research Institute), Ren-Hua Chung(National Health Research Institutes), Francis S. Collins(National Human Genome Research Institute), John Connell(University of Dundee), Angela Döring(Helmholtz Zentrum München), Jean Dallongeville(Inserm), John Danesh(University of Cambridge), Ulf dé Fairé(Karolinska Institutet), Graciela Delgado(Heidelberg University), Anna F. Dominiczak(University of Glasgow), Alex S. F. Doney(University of Dundee), Fotios Drenos(University College London), Sarah Edkins(Wellcome Sanger Institute), John D. Eicher(National Heart Lung and Blood Institute), Roberto Elosúa(Hospital del Mar Research Institute), Stefan Enroth(Uppsala University), Jeanette Erdmann(Institute for Integrative and Experimental Genomics), Per Eriksson(Karolinska Institutet), Tõnu Esko(Broad Institute), Εvangelos Εvangelou(University of Ioannina), Alun Evans(Queen's University Belfast), Tove Fall(Uppsala University), Martin Farrall(Centre for Human Genetics), Janine F. Felix(Erasmus MC), Jean Ferrières(Inserm), Luigi Ferrucci(National Institute on Aging), Myriam Fornage(The University of Texas Health Science Center at Houston), Terrence Forrester(University of the West Indies System), Nora Franceschini(University of North Carolina at Chapel Hill), Oscar H Franco Duran(Erasmus MC), Anders Franco‐Cereceda(University of Ioannina), Ross M. Fraser(University of Edinburgh), Santhi K. Ganesh(University of Michigan), He Gao(Imperial College London), Karl Gertow(Karolinska University Hospital), Francesco Gianfagna(University of Insubria), Bruna Gigante(Karolinska Institutet), Franco Giulianini(Brigham and Women's Hospital), Anuj Goel(Centre for Human Genetics), Alison H. Goodall(University of Leicester), Mark O Goodarzi(Cedars-Sinai Medical Center), Mathias Gorski(University Hospital Regensburg), Jürgen Gräßler(Technische Universität Dresden), Christopher J. Groves(University of Oxford), Vilmundur Guðnason(University of Iceland), Ulf Gyllensten(Uppsala University), Göran Hallmans(Umeå University), Anna-Liisa Hartikainen(Oulu University Hospital), Maija Hassinen(University of Eastern Finland), Aki S. Havulinna(Finnish Institute for Health and Welfare), Caroline Hayward(Western General Hospital), Serge Herçberg(Conservatoire National des Arts et Métiers), Karl-Heinz Herzig(Poznan University of Medical Sciences), Andrew A. Hicks(Eurac Research), Aroon D. Hingorani(MRC Epidemiology Unit), Joel N. Hirschhorn(Broad Institute), Albert Hofman(Harvard University), Jostein Holmen(Norwegian University of Science and Technology), Oddgeir L. Holmen(Norwegian University of Science and Technology), Jouke‐Jan Hottenga, Phil Howard(University College London), Chao A. Hsiung(National Health Research Institutes), Steven C. Hunt(University of Utah), M. Arfan Ikram(Erasmus MC), Thomas Illig(Helmholtz Zentrum München), Carlos Iribarren(Kaiser Permanente), Richard A. Jensen(University of Washington), Mika Kähönen(Tampere University Hospital), Hyun Min Kang(University of Michigan), Sekar Kathiresan(Broad Institute), Brendan J. Keating(University of Pennsylvania), Kay‐Tee Khaw(University of Cambridge), Yun Kyoung Kim(Korea National Institute of Health), Eric H. Kim(UCLA Medical Center), Mika Kivimäki(MRC Epidemiology Unit), Norman Klopp(Helmholtz Zentrum München), Genovefa Kolovou(Onassis Cardiac Surgery Center), Pirjo Komulainen(University of Eastern Finland), Jaspal S. Kooner(Imperial College Healthcare NHS Trust), Gülüm Kosova(Broad Institute), Ronald M. Krauss(Children’s Institute), Diana Kuh(MRC Unit for Lifelong Health and Ageing), Zoltán Kutalik(SIB Swiss Institute of Bioinformatics), Johanna Kuusisto(University of Eastern Finland), Kirsti Kvaløy(Norwegian University of Science and Technology), Timo A. Lakka(University of Eastern Finland), Sang Lee(University of San Carlos), I‐Te Lee(National Yang Ming Chiao Tung University), Wen‐Jane Lee(Taichung Veterans General Hospital), Daniel Levy(National Heart Lung and Blood Institute), Xiaohui Li(UCLA Medical Center), Kae-Woei Liang(National Yang Ming Chiao Tung University), Honghuang Lin(Boston University), Lin Li(University Hospital of Geneva), Jaana Lindström(Finnish Institute for Health and Welfare), Stéphane Lobbens(Centre National de la Recherche Scientifique), Satu Männistö(Finnish Institute for Health and Welfare), Gabriele Müller(University Hospital Carl Gustav Carus), Martina Müller‐Nurasyid(Zimmer Biomet (Netherlands)), François Mach(University Hospital of Geneva), Hugh S. Markus(University of Cambridge), Eirini Marouli(Queen Mary University of London), Mark I. McCarthy(University of Oxford), Colin A. McKenzie(University of the West Indies System), Pierre Meneton(Inserm), Cristina Menni(King's College London), Andres Metspalu(University of Tartu), Vladan Mijatovic(University of Verona), Leena Moilanen(Oulu University Hospital), May E. Montasser(University of Maryland, Baltimore), Andrew D Morris(Centre for Human Genetics), Alanna C. Morrison(The University of Texas Health Science Center at Houston), Antonella Mulas(Institute of Genetic and Biomedical Research), Ramaiah Nagaraja(Institute on Aging), Narisu Narisu(National Human Genome Research Institute), Kjell Nikus(Tampere University), Christopher J. O’Donnell(Massachusetts General Hospital), Paul F. O’Reilly(King's College London), Ken K. Ong(University of Cambridge), Fred Paccaud(University Hospital of Lausanne), Cameron D. Palmer(Broad Institute), Afshin Parsa(University of Maryland, Baltimore), Nancy L. Pedersen(Karolinska Institutet), Brenda W.J.H. Penninx(Leiden University), Markus Perola(Finnish Institute for Health and Welfare), Annette Peters(Helmholtz Zentrum München), Neil Poulter(Imperial College London), Peter P. Pramstaller(Eurac Research), Bruce M. Psaty(Group Health Cooperative), Thomas Quertermous(Stanford University), Dabeeru C Rao(Washington University in St. Louis), Asif Rasheed(Center for Non-Communicable Diseases), N. William Rayner(Centre for Human Genetics), Frida Renström(Harvard University), Rainer Rettig(Universitätsmedizin Greifswald), Kenneth Rice(University of Washington), Robert Roberts(Canadian Heart Research Centre), Lynda M. Rose(Brigham and Women's Hospital), Jacques Rossouw(National Heart Lung and Blood Institute), Nilesh J. Samani(University of Leicester), Serena Sanna(Institute of Genetic and Biomedical Research), Jouko Saramies(South Karelia Central Hospital), Heribert Schunkert(Deutsches Herzzentrum der Charité), Sylvain Sebért(Kuopio University Hospital), Wayne H-H Sheu(National Yang Ming Chiao Tung University), Young-Ah Shin(Korea National Institute of Health), Xueling Sim(National University of Singapore), Johannes H. Smit(Amsterdam Public Health), Albert V. Smith(University of Iceland), Maria X. Sosa(Johns Hopkins University), Tim D. Spector(King's College London), Alena Stančáková(University of Eastern Finland), Alice Stanton(University College Dublin), Kathleen Stirrups(Queen Mary University of London), Heather M. Stringham(University of Michigan), Johan Sundström(Uppsala University), Amy J. Swift(National Human Genome Research Institute), Ann‐Christine Syvänen(Uppsala University), E Shyong Tai(National University of Singapore), Toshiko Tanaka(National Institute on Aging), Kirill V. Tarasov(Institute on Aging), Alexander Teumer(Universitätsmedizin Greifswald), Unnur Thorsteinsdottir(deCODE Genetics (Iceland)), Martin D. Tobin(University of Leicester), Elena Tremoli(University of Milan), André G. Uitterlinden(Erasmus MC), Matti Uusitupa(University of Eastern Finland), Ahmad Vaez(Isfahan University of Medical Sciences), Dhananjay Vaidya(Johns Hopkins University), Cornelia M. van Duijn(Erasmus MC), Erik P.A. van Iperen(Amsterdam UMC Location University of Amsterdam), Ramachandran S. Vasan(Boston University), Germaine C. Verwoert(Erasmus MC), Jarmo Virtamo(Finnish Institute for Health and Welfare), Véronique Vitart(Western General Hospital), Benjamin F. Voight(Broad Institute), Péter Vollenweider(University of Lausanne), Aline Wagner(Université de Strasbourg), Louise V. Wain(University of Leicester), Nicholas J. Wareham(University of Cambridge), Hugh Watkins(Centre for Human Genetics), Alan B. Weder(University of Michigan), Harm-Jan Westra(University Medical Center Groningen), Rainford Wilks(University of the West Indies System), Tom Wilsgaard(UiT The Arctic University of Norway), James F Wilson(Western General Hospital), Tien Yin Wong(Singapore National Eye Center), Tsun-Po Yang(Queen Mary University of London), Jie Yao(UCLA Medical Center), Loïc Yengo(Centre National de la Recherche Scientifique), Weihua Zhang(Ealing Hospital), Jing Hua Zhao(University of Cambridge), Xiaofeng Zhu(Case Western Reserve University), Pascal Bovet(University Hospital of Lausanne), Richard S Cooper(Loyola University Chicago), Karen L Mohlke(University of North Carolina at Chapel Hill), Danish Saleheen(Center for Non-Communicable Diseases), Jong‐Young Lee(Korea National Institute of Health), Paul Elliott(Public Health England), Hinco J. Gierman(Illumina (United States)), Cristen J. Willer(University of Michigan), Lude Franke(University Medical Center Groningen), G. Kees Hovingh(Amsterdam UMC Location University of Amsterdam), Kent D. Taylor(UCLA Medical Center), George Dedoussis(Harokopio University of Athens), Peter S. Sever(Imperial College London), Andrew Wong(MRC Unit for Lifelong Health and Ageing), Lars Lind(Uppsala University), Themistocles L. Assimes(Stanford University), Inger Njølstad(UiT The Arctic University of Norway), Peter E. H. Schwarz(University Hospital Carl Gustav Carus), Claudia Langenberg(University of Cambridge), Harold Snieder(University Medical Center Groningen), Mark J. Caulfield(Queen Mary University of London), Olle Melander(Malmö University), Markku Laakso(University of Eastern Finland), Juha Saltevo(Central Finland Health Care District), Rainer Rauramaa(University of Eastern Finland), Jaakko Tuomilehto(Universität für Weiterbildung Krems), Erik Ingelsson(Uppsala University), Terho Lehtimäki(Tampere University), Kristian Hveem(Norwegian University of Science and Technology), Walter Palmas(Columbia University), Winfried März(Synlab Czech (Czechia)), Meena Kumari(MRC Epidemiology Unit), Veikko Salomaa(Finnish Institute for Health and Welfare), Yii‐Der I. Chen(UCLA Medical Center), Jerome I. Rotter(UCLA Medical Center), Philippe Froguel(Centre National de la Recherche Scientifique), Marjo‐Riitta Järvelin(Oulu University Hospital), Edward G. Lakatta(Institute on Aging), Kari Kuulasmaa(Finnish Institute for Health and Welfare), Paul W. Franks(Harvard University), Anders Hamsten(Karolinska University Hospital), H-Erich Wichmann(Zimmer Biomet (Netherlands)), Colin N A Palmer(Broad Institute), Kāri Stefánsson(deCODE Genetics (Iceland)), Paul M. Ridker(Brigham and Women's Hospital), Ruth J. F. Loos(University of Cambridge), Aravinda Chakravarti(Johns Hopkins University), Panos Deloukas(Queen Mary University of London), Andrew P. Morris(Centre for Human Genetics), Christopher Newton‐Cheh(Broad Institute), Patricia B. Munroe(Queen Mary University of London)
Cited by 437Open Access
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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