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

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Title: 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
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 (CHARGE) BP Exome Consortium
International Genomics of Blood Pressure (iGEN-BP) Consortium
UK Biobank CardioMetabolic Consortium BP working group
Item Type: Journal Article
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.
Issue Date: 30-Jan-2017
Date of Acceptance: 14-Dec-2016
URI: http://hdl.handle.net/10044/1/44681
DOI: https://dx.doi.org/10.1038/ng.3768
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 403
End Page: 415
Journal / Book Title: Nature Genetics
Volume: 49
Issue: 3
Copyright Statement: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/ng.3768
Sponsor/Funder: UK Biobank
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
British Heart Foundation
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: PO 9540
NF-SI-0611-10136
RDC01 79560
SP/13/2/30111
MR/L01632X/1
MR/L01341X/1
RTJ6219303-1
Keywords: Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Conference Place: United States
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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