Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg 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.
Bibliographical noteFunding Information:
47Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Uppal Road, Hyderabad 500 007, India. 48Department of Public Health andPrimaryCare,UniversityofCambridge,CB18RN,UK.49DepartmentofBasicMedical Research and Education, and Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan. 50Division of Community Health Sciences, St George’s University of London, London SW17 0RE, UK. 51Epidemiology & Prevention,Division ofPublic Health Sciences, Wake Forest University Schoolof Medicine, Winston-Salem,NorthCarolina27157,USA.52DivisionofBiostatisticsandDepartmentof Genetics, School of Medicine, Washington University in St. Louis, Saint Louis, Missouri 63110, USA. 53Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland. 54Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA. 55Department of Laboratory Medicine & Institute of Human Genetics, University of California San Francisco, 513 Parnassus Ave. San Francisco, California 94143, USA. 56Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore138672,Singapore.57CentreforMolecularEpidemiology,YongLooLinSchool of Medicine, National University of Singapore, Singapore 117597, Singapore. 58Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere 33521, Finland. 59Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, 10126 Torino, Italy. 60Human Genetics Foundation (HUGEF), Via Nizza 52, 10126 Torino, Italy. 61Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 62MRC Centre for Causal Analyses in TranslationalEpidemiology, School ofSocial& Community Medicine,University ofBristol, Bristol BS8 2BN, UK. 63Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA Utrecht, The Netherlands.