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Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
Authors:International Consortium for Blood Pressure Genome-Wide Association Studies  Ehret Georg B  Munroe Patricia B  Rice Kenneth M  Bochud Murielle  Johnson Andrew D  Chasman Daniel I  Smith Albert V  Tobin Martin D  Verwoert Germaine C  Hwang Shih-Jen  Pihur Vasyl  Vollenweider Peter  O'Reilly Paul F  Amin Najaf  Bragg-Gresham Jennifer L  Teumer Alexander  Glazer Nicole L  Launer Lenore  Zhao Jing Hua  Aulchenko Yurii  Heath Simon  Sõber Siim  Parsa Afshin  Luan Jian'an  Arora Pankaj  Dehghan Abbas  Zhang Feng  Lucas Gavin  Hicks Andrew A  Jackson Anne U  Peden John F  Tanaka Toshiko  Wild Sarah H  Rudan Igor  Igl Wilmar
Abstract:Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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