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Article Dans Une Revue Nature Genetics Année : 2016

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

Georg B. Ehret (1, 2, 3) , Teresa Ferreira (4) , Daniel I. Chasman (5, 6) , Anne U. Jackson (7, 8) , Ellen M. Schmidt (9) , Toby Johnson (10, 11) , Gudmar Thorleifsson (12) , Jian'An Luan (13) , Louise A. Donnelly (14) , Stavroula Kanoni (10) , Ann -Kristin Petersen (15) , Vasyl Pihurl (1) , Rona J. Strawbridge (16) , Dmitry Shungin (17, 18) , Maria F. Hughes (19) , Osorio Meirelles (20) , Marika Kaakinen (21) , Nabila Bouatia-Naji (22, 23) , Kati Kristiansson (24, 25) , Sonia Shah (26) , Marcus E. Kleber (27) , Xiuqing Guo (28) , Leo-Pekka Lyytikäinen (29) , Cristiano Fava (18, 30) , Nidas Eriksson (31) , Ilja M. Nolte (32) , Patrik K. Magnusson (33) , Elias L. Salfati (34) , Loukianos S. Rallidis (35) , Elizabeth Theusch (36) , Andrew J. P. Smith (26) , Lasse Folkersen (37) , Kate Witkowska (10) , Tune H. Pers (38, 39, 40, 41) , Roby Joehanes (42) , Stuart K. Kim (34) , Lazaros Lataniotis (10) , Rick Jansen (43) , Andrew D. Johnson (42, 44) , Helen Warren (10) , Young Jin Kim (45) , Wei Zhao (46) , Ying Wu (47) , Bamidele O. Tayo (48) , Murielle Bochud (49) , Devin Absher (50) , Linda S. Adair (51) , Najaf Amin (52) , Dan E. Arkingl (1) , Tomas Axelsson (53) , Damian Baldassarre (54, 55) , Beverley Balkau (56) , Stefania Bandinelli (57) , Michael R. Barnes (10) , Inês Barroso (13, 58) , Stephen Bevan (59) , Joshua C. Bis (60) , Gyda Bjornsdottir (61) , Michael Boehnke (8) , Eric Boerwinkle (62) , Lori L. Bonnycastle (20) , Dorret I. Boomsma (63) , Stefan R. Bornstein (64) , Morris J. Brown (10) , Michel Burnier (65, 49) , Claudia P. Cabrera (10) , John C. Chambers (66, 67) , I-Shou Chang (68) , Ching-Yu Cheng (69, 70, 71, 72) , Peter S. Chines (73) , Ren-Hua Chung (68) , Francis S. Collins (20) , John M. Connell , Angela Döring , Jean Dallongeville , John Danesh (58) , Ulf de Faire , Graciela Delgado , Anna F. Dominiczak , Alex S. F. Doney , Fotios Drenos , Sarah Edkins (58) , John D. Eicher , Roberto Elosua , Stefan Enroth , Jeanette Erdmann , Per Eriksson (37) , Tonu Esko (38) , Evangelos Evangelou , Alun Evans (19) , Tove Fai , Martin Farrall (4) , Janine F. Felixl , Jean Ferrières , Luigi Ferrucci , Myriam Fornage , Terrence Forrester , Nora Franceschinil , Oscar H. Franco , Anders Franco-Cereceda , Ross M. Fraser , Serge Hercberg (74) , Pierre Meneton (75)
1 Johns Hopkins University, School of Medicine
2 HUG - Hôpitaux Universitaires de Genève
3 Saw Swee Hock School of Public Health
4 The Wellcome Trust Centre for Human Genetics [Oxford]
5 Brigham and Women's Hospital [Boston]
6 HMS - Harvard Medical School [Boston]
7 Department of Biostatistics
8 University of Michigan [Ann Arbor]
9 DCM&B - Department of Computational Medicine and Bioinformatics
10 QMUL - Queen Mary University of London
11 GlaxoSmithKline
12 deCODE genetics [Reykjavik]
13 CAM - University of Cambridge [UK]
14 University of Dundee
15 German Research Center for Environmental Health - Helmholtz Center München (GmbH)
16 Karolinska University Hospital [Stockholm]
17 Nus - Umeå University Hospital = Norrlands universitetssjukhus
18 Skane University Hospital [Lund]
19 QUB - Queen's University [Belfast]
20 NIH - National Institutes of Health [Bethesda, MD, USA]
21 Department of Genomics of Common Disease
22 INSERM - Institut National de la Santé et de la Recherche Médicale
23 UPD5 - Université Paris Descartes - Paris 5
24 National Institute of Health and Welfare
25 Institute for Molecular Medicine Finland (FIMM)
26 UCLH - University College London Hospitals
27 University Hospital of Heidelberg
28 Harbor UCLA Medical Center [Torrance, Ca.]
29 University of Tampere
30 UNIVR - Università degli studi di Verona = University of Verona
31 Uppsala University Hospital
32 University of Groningen [Groningen]
33 MEB - Department of Medical Epidemiology and Biostatistics
34 Stanford University School of Medicine [CA, USA]
35 Medical School University of Athens
36 Children's Hospital Oakland Research Institute
37 Karolinska Institutet [Stockholm]
38 Boston Children's Hospital
39 Broad Institute of Harvard and MIT
40 UCPH - University of Copenhagen = Københavns Universitet
41 Statens Serum Institut [Copenhagen]
42 Framingham Heart Dis Epidemiol Study
43 Department of Psychiatry
44 National Heart, Lung and Blood Institute
45 Osong Health Technology Administration Complex
46 University of Pennsylvania
47 Department of Genetics
48 Loyola University [Chicago]
49 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
50 Hudson Alpha Institute for Biotechnology
51 UNC - University of North Carolina at Chapel Hill
52 Erasmus University Rotterdam
53 Department of Medical Sciences
54 UNIMI - Università degli Studi di Milano = University of Milan
55 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico
56 UP11 - Université Paris-Sud - Paris 11
57 Azienda Sanitaria Firenze
58 Wellcome Trust Genome Campus
59 University of Lincoln [UK]
60 University of Washington [Seattle]
61 AMGen - Applied Molecular Genetics
62 UTHealth - The University of Texas Health Science Center at Houston
63 VU - Vrije Universiteit Amsterdam [Amsterdam]
64 University of Dresden Medical School
65 UNIL - Université de Lausanne = University of Lausanne
66 Healthcare NHS Trust
67 Imperial College London
68 National Health Research Institutes
69 NUHS - National University Health System [Singapore]
70 NUS - National University of Singapore
71 Duke-NUS Medical School [Singapore]
72 SERI - Singapore Eye Research Institute [Singapore]
73 NHGRI - National Human Genome Research Institute
74 CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité
75 LIMICS - Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé
Ying Wu
John M. Connell
  • Fonction : Auteur
Angela Döring
  • Fonction : Auteur
Jean Dallongeville
  • Fonction : Auteur
Ulf de Faire
  • Fonction : Auteur
Graciela Delgado
  • Fonction : Auteur
Anna F. Dominiczak
  • Fonction : Auteur
Alex S. F. Doney
  • Fonction : Auteur
Fotios Drenos
  • Fonction : Auteur
John D. Eicher
  • Fonction : Auteur
Roberto Elosua
  • Fonction : Auteur
Stefan Enroth
  • Fonction : Auteur
Jeanette Erdmann
Evangelos Evangelou
  • Fonction : Auteur
Tove Fai
  • Fonction : Auteur
Janine F. Felixl
  • Fonction : Auteur
Jean Ferrières
Luigi Ferrucci
  • Fonction : Auteur
Myriam Fornage
  • Fonction : Auteur
Terrence Forrester
  • Fonction : Auteur
Nora Franceschinil
  • Fonction : Auteur
Oscar H. Franco
  • Fonction : Auteur
Anders Franco-Cereceda
  • Fonction : Auteur
Ross M. Fraser
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-02639685 , version 1 (28-05-2020)

Identifiants

Citer

Georg B. Ehret, Teresa Ferreira, Daniel I. Chasman, Anne U. Jackson, Ellen M. Schmidt, et al.. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics, 2016, 48 (10), pp.1171-1184. ⟨10.1038/ng.3667⟩. ⟨hal-02639685⟩
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