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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
File | Description | Size | Format | |
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Warren et al_UKB-BP_PrePrint.pdf | Accepted version | 1.06 MB | Adobe PDF | View/Open |
WarrenHR_NG-A44289_SupNote_ProofsHRW_noICBP_v2.pdf | Supporting information | 7.98 MB | Adobe PDF | View/Open |
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 |