Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
;
Claudia P Cabrera;
He Gao;
Meixia Ren;
Borbala Mifsud;
Ioanna Ntalla;
Praveen Surendran;
Chunyu Liu;
James P Cook;
+60 more...
Aldi T Kraja;
Fotios Drenos;
Marie Loh;
Niek Verweij;
Jonathan Marten;
Ibrahim Karaman ;
Marcelo P Segura Lepe;
Paul F O'Reilly;
Joanne Knight;
Harold Snieder;
Norihiro Kato;
Jiang He;
E Shyong Tai;
M Abdullah Said;
David Porteous ;
Maris Alver;
Neil Poulter;
Martin Farrall;
Ron T Gansevoort;
Sandosh Padmanabhan;
Reedik Mägi;
Alice Stanton ;
John Connell;
Stephan JL Bakker;
Andres Metspalu;
Denis C Shields;
Simon Thom ;
Morris Brown;
Peter Sever;
Tõnu Esko;
Caroline Hayward;
Pim van der Harst;
Danish Saleheen;
Rajiv Chowdhury;
John C Chambers;
Daniel I Chasman;
Aravinda Chakravarti;
Christopher Newton-Cheh;
Cecilia M Lindgren;
Daniel Levy;
Jaspal S Kooner;
Bernard Keavney ;
Maciej Tomaszewski;
Nilesh J Samani;
Joanna MM Howson;
Martin D Tobin;
Patricia B Munroe;
Georg B Ehret ;
Louise V Wain ;
International Consortium of Blood Pressure (ICBP) 1000G Analyses;
BIOS Consortium;
Lifelines Cohort Study;
Understanding Society Scientific group;
CHD Exome+ Consortium;
ExomeBP Consortium;
T2D-GENES Consortium;
GoT2DGenes Consortium;
Cohorts for Heart and Ageing Research in Genome Epidemiology (CH;
International Genomics of Blood Pressure (iGEN-BP) Consortium;
UK Biobank CardioMetabolic Consortium BP working group;
(2017)
Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
Nature genetics, 49 (3).
pp. 403-415.
ISSN 1061-4036
DOI: 10.1038/ng.3768
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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subject - Accepted Version
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- Available under Creative Commons: NC-ND 3.0