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

Helen R. Warren, Evangelos Evangelou, Claudia P. Cabrera, He Gao, Meixia Ren, Borbala Mifsud, Ioanna Ntalla, Praveen Surendran, Chunyu Liu, James P. Cook, Aldi T. Kraja, Fotios Drenos, Marie Loh, Niek Verweij, Jonathan Marten, Ibrahim Karaman, Marcelo P. Segura Lepe, Paul F. O'Reilly, Joanne Knight, Harold SniederNorihiro 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 J. L. 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 M. M. Howson, Martin D. Tobin, Patricia B. Munroe, Georg B. Ehret, Louise V. Wain, Alan J. Gow, The International Consortium of Blood Pressure (ICBP) 1000G Analyses, The CHD Exome+ Consortium, The ExomeBP Consortium, The T2D-GENES Consortium, The GoT2DGenes Consortium, The Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium, The International Genomics of Blood Pressure (iGEN -BP) Consortium, for The UK Biobank CardioMetabolic Consortium BP working group Louise

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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.

Original languageEnglish
Pages (from-to)403-415
Number of pages13
JournalNature Genetics
Volume49
Issue number3
Early online date30 Jan 2017
DOIs
Publication statusPublished - 1 Mar 2017

ASJC Scopus subject areas

  • Genetics

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    Warren, H. R., Evangelou, E., Cabrera, C. P., Gao, H., Ren, M., Mifsud, B., Ntalla, I., Surendran, P., Liu, C., Cook, J. P., Kraja, A. T., Drenos, F., Loh, M., Verweij, N., Marten, J., Karaman, I., Segura Lepe, M. P., O'Reilly, P. F., Knight, J., ... for The UK Biobank CardioMetabolic Consortium BP working group Louise (2017). Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nature Genetics, 49(3), 403-415. https://doi.org/10.1038/ng.3768