Warren, Helen R. and Evangelou, Evangelos and Cabrera, Claudia P. and Gao, He and Ren, Meixia and Mifsud, Borbala and Ntalla, Ioanna and Surendran, Praveen and Liu, Chunyu and Cook, James P. and Kraja, Aldi T. and Drenos, Fotios and Loh, Marie and Verweij, Niek and Marten, Jonathan and Karaman, Ibrahim and Lepe, Marcelo P. Segura and O'Reilly, Paul F. and Knight, Joanne and Snieder, Harold and Kato, Norihiro and He, Jiang and Tai, E. Shyong and Said, M. Abdullah and Porteous, David and Alver, Maris and Poulter, Neil and Farrall, Martin and Gansevoort, Ron T. and Padmanabhan, Sandosh and Mägi, Reedik and Stanton, Alice and Connell, John and Bakker, Stephan J. L. and Metspalu, Andres and Shields, Denis C. and Thom, Simon and Brown, Morris and Sever, Peter and Esko, Tõnu and Hayward, Caroline and van der Harst, Pim and Saleheen, Danish and Chowdhury, Rajiv and Chambers, John C. and Chasman, Daniel I. and Chakravarti, Aravinda and Newton-Cheh, Christopher and Lindgren, Cecilia M. and Levy, Daniel and International Consortium of Blood Pressure (ICBP) 1000G Analyses (2017) Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nature Genetics, 49. pp. 403-415. ISSN 1061-4036
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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.