title: Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.
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.
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Warren
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
authors.forename: Evangelos
authors.identifier: http://orcid.org/0000-0002-5488-2999
authors.initials: E
authors.lastname: Evangelou
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Claudia P
authors.initials: CP
authors.lastname: Cabrera
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
authors.forename: He
authors.initials: H
authors.lastname: Gao
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Meixia
authors.initials: M
authors.lastname: Ren
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Borbala
authors.initials: B
authors.lastname: Mifsud
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ntalla
authors.affiliation: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Praveen
authors.initials: P
authors.lastname: Surendran
authors.affiliation: Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.|Boston University School of Public Health, Boston, Massachusetts, USA.|National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Cook
authors.affiliation: Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Aldi T
authors.initials: AT
authors.lastname: Kraja
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.|Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Marie
authors.initials: M
authors.lastname: Loh
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.|Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Niek
authors.initials: N
authors.lastname: Verweij
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Marten
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
authors.forename: Ibrahim
authors.identifier: http://orcid.org/0000-0001-9341-8155
authors.initials: I
authors.lastname: Karaman
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|Bayer Pharma, Berlin, Germany.
authors.forename: Marcelo P Segura
authors.initials: MP
authors.lastname: Lepe
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Paul F
authors.initials: PF
authors.lastname: O'Reilly
authors.affiliation: Data Science Institute, Lancester University, Lancaster, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Knight
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.affiliation: Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
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authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
authors.forename: Jiang
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authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: M Abdullah
authors.initials: MA
authors.lastname: Said
authors.affiliation: Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: David
authors.identifier: http://orcid.org/0000-0003-1249-6106
authors.initials: D
authors.lastname: Porteous
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Maris
authors.initials: M
authors.lastname: Alver
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK.
authors.forename: Neil
authors.initials: N
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authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nephrology, Groningen, the Netherlands.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Sandosh
authors.initials: S
authors.lastname: Padmanabhan
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Reedik
authors.initials: R
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authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Alice
authors.identifier: http://orcid.org/0000-0002-4961-165X
authors.initials: A
authors.lastname: Stanton
authors.affiliation: Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: John
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authors.lastname: Connell
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, the Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Denis C
authors.initials: DC
authors.lastname: Shields
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Simon
authors.identifier: http://orcid.org/0000-0002-3020-1351
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authors.lastname: Thom
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Morris
authors.initials: M
authors.lastname: Brown
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Sever
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Centre for Non-Communicable Diseases, Karachi, Pakistan.|Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Danish
authors.initials: D
authors.lastname: Saleheen
authors.affiliation: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.|Ealing Hospital National Health Service (NHS) Trust, Southall, UK.|Imperial College Healthcare NHS Trust, London, UK.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: John C
authors.initials: JC
authors.lastname: Chambers
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.|Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.affiliation: Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.|Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.affiliation: Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.|National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
authors.forename: Daniel
authors.initials: D
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authors.affiliation: Imperial College Healthcare NHS Trust, London, UK.|Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.|National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London, London, UK.
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Kooner
authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Bernard
authors.identifier: http://orcid.org/0000-0001-9573-0812
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authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Maciej
authors.initials: M
authors.lastname: Tomaszewski
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Leicester, UK.|NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Nilesh J
authors.initials: NJ
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authors.affiliation: Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Joanna M M
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authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.affiliation: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.|National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
authors.forename: Patricia B
authors.initials: PB
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authors.affiliation: Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Cardiology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Georg B
authors.identifier: http://orcid.org/0000-0002-5730-0675
authors.initials: GB
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authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.
authors.forename: Louise V
authors.identifier: http://orcid.org/0000-0003-4951-1867
authors.initials: LV
authors.lastname: Wain
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics