Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

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Michael G Marmot ; Tetsuro Miki ; Danish Saleheen ; Giriraj R Chandak ; Josef Coresh ; Gerjan Navis ; Veikko Salomaa ; Bok-Ghee Han ; Xiaofeng Zhu ; Jaspal S Kooner ; Olle Melander ; Paul M Ridker ; Stefania Bandinelli ; Ulf B Gyllensten ; Alan F Wright ; James F Wilson ; Luigi Ferrucci ; Martin Farrall ; Jaakko Tuomilehto ; Peter P Pramstaller ; Roberto Elosua ; Nicole Soranzo ; Eric JG Sijbrands ; David Altshuler ; Ruth JF Loos ; Alan R Shuldiner ; Christian Gieger ; Pierre Meneton ; Andre G Uitterlinden ; Nicholas J Wareham ; Vilmundur Gudnason ; Jerome I Rotter ; Rainer Rettig ; Manuela Uda ; David P Strachan ; Jacqueline CM Witteman ; Anna-Liisa Hartikainen ; Jacques S Beckmann ; Eric Boerwinkle ; Ramachandran S Vasan ; Michael Boehnke ; Martin G Larson ; Marjo-Riitta Järvelin ; Bruce M Psaty ; Gonçalo R Abecasis ; Aravinda Chakravarti ; Paul Elliott ; Cornelia M van Duijn ; Christopher Newton-Cheh ; Daniel Levy ; Mark J Caulfield ; Toby Johnson ; (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478 (7367). pp. 103-109. ISSN 0028-0836 DOI: 10.1038/nature10405
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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.
Item Type Article
ISI 295575400043
Date Deposited 03 Jun 2013 12:03

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