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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk | Nature Genetics
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Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension. 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.
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headline:Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
description:Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension. 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 pressureâraising genetic variants on future cardiovascular disease risk.
datePublished:2017-01-30T00:00:00Z
dateModified:2017-10-01T00:00:00Z
pageStart:403
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sameAs:https://doi.org/10.1038/ng.3768
keywords:
Genome-wide association studies
Hypertension
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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headline:Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
description:Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension. 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 pressureâraising genetic variants on future cardiovascular disease risk.
datePublished:2017-01-30T00:00:00Z
dateModified:2017-10-01T00:00:00Z
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Genome-wide association studies
Hypertension
Biomedicine
general
Human Genetics
Cancer Research
Agriculture
Gene Function
Animal Genetics and Genomics
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name:National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London
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name:Peter Sever
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address:
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type:Organization
name:Pim van der Harst
affiliation:
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address:
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type:Organization
name:Danish Saleheen
affiliation:
name:Perelman School of Medicine, University of Pennsylvania
address:
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type:PostalAddress
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name:Centre for Non-Communicable Diseases
address:
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name:University of Cambridge
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type:PostalAddress
type:Organization
name:Rajiv Chowdhury
affiliation:
name:Cardiovascular Epidemiology Unit, University of Cambridge
address:
name:Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK
type:PostalAddress
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name:John C Chambers
affiliation:
name:School of Public Health, Imperial College London
address:
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type:PostalAddress
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name:Ealing Hospital National Health Service (NHS) Trust
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name:Imperial College Healthcare NHS Trust
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type:PostalAddress
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name:Lee Kong Chian School of Medicine, Nanyang Technological University
address:
name:Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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name:Daniel I Chasman
affiliation:
name:Brigham and Women's Hospital
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address:
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address:
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name:Georg B Ehret
url:http://orcid.org/0000-0002-5730-0675
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address:
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affiliation:
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address:
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type:PostalAddress
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PostalAddress:
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK
name:Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
name:Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK
name:Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
name:MRC-PHE Centre for Environment and Health, Imperial College London, London, UK
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK
name:Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
name:Boston University School of Public Health, Boston, USA
name:National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, USA
name:Department of Biostatistics, University of Liverpool, Liverpool, UK
name:Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, USA
name:MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK
name:Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK
name:Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
name:Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore
name:Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
name:Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA
name:Center for Human Genetic Research, Massachusetts General Hospital, Boston, USA
name:Cardiovascular Research Center, Massachusetts General Hospital, Boston, USA
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name:Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
name:Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
name:Bayer Pharma, Berlin, Germany
name:Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
name:Data Science Institute, Lancester University, Lancaster, UK
name:Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
name:Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
name:Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, USA
name:Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore
name:Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
name:Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
name:Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
name:Estonian Genome Center, University of Tartu, Tartu, Estonia
name:Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK
name:Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
name:Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
name:Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
name:Estonian Genome Center, University of Tartu, Tartu, Estonia
name:Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
name:Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
name:Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
name:Estonian Genome Center, University of Tartu, Tartu, Estonia
name:School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland
name:National Heart and Lung Institute, Imperial College London, London, UK
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK
name:National Heart and Lung Institute, Imperial College London, London, UK
name:Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA
name:Estonian Genome Center, University of Tartu, Tartu, Estonia
name:MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
name:Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
name:Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
name:Centre for Non-Communicable Diseases, Karachi, Pakistan
name:Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
name:Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK
name:Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
name:Ealing Hospital National Health Service (NHS) Trust, Southall, UK
name:Imperial College Healthcare NHS Trust, London, UK
name:Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
name:Division of Preventive Medicine, Brigham and Women's Hospital, Boston, USA
name:Harvard Medical School, Boston, USA
name:Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, USA
name:Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA
name:Center for Human Genetic Research, Massachusetts General Hospital, Boston, USA
name:Cardiovascular Research Center, Massachusetts General Hospital, Boston, USA
name:Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, USA
name:Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
name:Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
name:Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
name:National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, USA
name:Imperial College Healthcare NHS Trust, London, UK
name:Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK
name:National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London, London, UK
name:Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
name:Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
name:Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
name:Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
name:Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK
name:NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK
name:Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, UK
name:Department of Health Sciences, University of Leicester, Leicester, UK
name:William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
name:National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK
name:Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, USA
name:Department of Medicine, Cardiology, Geneva University Hospital, Geneva, Switzerland
name:Department of Health Sciences, University of Leicester, Leicester, UK
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