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Nat Genet. 2017 Mar;49(3):403-415. doi: 10.1038/ng.3768. Epub 2017 Jan 30.

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

Author information

1
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
2
National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
3
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
4
Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
5
MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
6
Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
7
Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
8
Boston University School of Public Health, Boston, Massachusetts, USA.
9
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
10
Department of Biostatistics, University of Liverpool, Liverpool, UK.
11
Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
12
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
13
Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
14
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore.
15
University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
16
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
17
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
18
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
19
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
20
Bayer Pharma, Berlin, Germany.
21
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
22
Data Science Institute, Lancester University, Lancaster, UK.
23
University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
24
Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
25
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
26
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
27
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
28
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
29
Estonian Genome Center, University of Tartu, Tartu, Estonia.
30
Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK.
31
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
32
University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, the Netherlands.
33
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
34
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
35
Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
36
University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, the Netherlands.
37
School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
38
National Heart and Lung Institute, Imperial College London, London, UK.
39
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
40
Centre for Non-Communicable Diseases, Karachi, Pakistan.
41
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
42
Ealing Hospital National Health Service (NHS) Trust, Southall, UK.
43
Imperial College Healthcare NHS Trust, London, UK.
44
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
45
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
46
Harvard Medical School, Boston, Massachusetts, USA.
47
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
48
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
49
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
50
Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.
51
National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London, London, UK.
52
Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
53
Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
54
Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.
55
NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
56
Department of Health Sciences, University of Leicester, Leicester, UK.
57
Cardiology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.

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.

PMID:
28135244
PMCID:
PMC5972004
DOI:
10.1038/ng.3768
[Indexed for MEDLINE]
Free PMC Article

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