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

Authors :
Warren HR
Evangelou E
Cabrera CP
Gao H
Ren M
Mifsud B
Ntalla I
Surendran P
Liu C
Cook JP
Kraja AT
Drenos F
Loh M
Verweij N
Marten J
Karaman I
Lepe MP
O'Reilly PF
Knight J
Snieder H
Kato N
He J
Tai ES
Said MA
Porteous D
Alver M
Poulter N
Farrall M
Gansevoort RT
Padmanabhan S
Mägi R
Stanton A
Connell J
Bakker SJ
Metspalu A
Shields DC
Thom S
Brown M
Sever P
Esko T
Hayward C
van der Harst P
Saleheen D
Chowdhury R
Chambers JC
Chasman DI
Chakravarti A
Newton-Cheh C
Lindgren CM
Levy D
Kooner JS
Keavney B
Tomaszewski M
Samani NJ
Howson JM
Tobin MD
Munroe PB
Ehret GB
Wain LV
Source :
Nature genetics [Nat Genet] 2017 Mar; Vol. 49 (3), pp. 403-415. Date of Electronic Publication: 2017 Jan 30.
Publication Year :
2017

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.

Details

Language :
English
ISSN :
1546-1718
Volume :
49
Issue :
3
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
28135244
Full Text :
https://doi.org/10.1038/ng.3768