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

Helen R Warren; Evangelos Evangelou; Claudia P Cabrera; He Gao; Meixia Ren; Borbala Mifsud; Ioanna Ntalla; Praveen Surendran; Chunyu Liu; James P Cook; Aldi T Kraja; Fotios Drenos; Marie Loh; Niek Verweij; Jonathan Marten; Ibrahim Karaman; Marcelo P Segura Lepe; Paul F O'Reilly; Joanne Knight; Harold Snieder; Norihiro Kato; Jiang He; E Shyong Tai; M Abdullah Said; David Porteous; Maris Alver; Neil Poulter; Martin Farrall; Ron T Gansevoort; Sandosh Padmanabhan; Reedik Mägi; Alice Stanton; John Connell; Stephan J L Bakker; Andres Metspalu; Denis C Shields; Simon Thom; Morris Brown; Peter Sever; Tõnu Esko; Caroline Hayward; Pim van der Harst; Danish Saleheen; Rajiv Chowdhury; John C Chambers; Daniel I Chasman; Aravinda Chakravarti; Christopher Newton-Cheh; Cecilia M Lindgren; Daniel Levy; Jaspal S Kooner; Bernard Keavney; Maciej Tomaszewski; Nilesh J Samani; Joanna M M Howson; Martin D Tobin; Patricia B Munroe; Georg B Ehret; Louise V Wain; International Consortium of Blood Pressure (ICBP) 1000G Analyses; Jaakko Tuomilehto

doi:10.1038/ng.3768

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

Journal article

Peer reviewed

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

Helen R Warren, Evangelos Evangelou, Claudia P Cabrera, He Gao, Meixia Ren, Borbala Mifsud, Ioanna Ntalla, Praveen Surendran, Chunyu Liu, James P Cook, …

Nature genetics, Vol.49(3), pp.403-415

01/03/2017

DOI: https://doi.org/10.1038/ng.3768

PMCID: PMC5972004

PMID: 28135244

Abstract

Adult

Blood Pressure - genetics

Cardiovascular Diseases - genetics

Female

Genetic Loci - genetics

Genetic Predisposition to Disease - genetics

Genome-Wide Association Study - methods

Humans

Hypertension - genetics

Male

Middle Aged

Polymorphism, Single Nucleotide - genetics

Risk Factors

Whites - genetics

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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Title: Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
Creators - without role: Helen R Warren - Queen Mary University of London
Evangelos Evangelou - University of Ioannina
Claudia P Cabrera - Queen Mary University of London
He Gao - Imperial College London
Meixia Ren - Queen Mary University of London
Borbala Mifsud - Queen Mary University of London
Ioanna Ntalla - Queen Mary University of London
Praveen Surendran - University of Cambridge
Chunyu Liu - National Heart Lung and Blood Institute
James P Cook - University of Liverpool
Aldi T Kraja - Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA
Fotios Drenos - University College London
Marie Loh - Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), Singapore
Niek Verweij - Massachusetts General Hospital
Jonathan Marten - University of Edinburgh
Ibrahim Karaman - Imperial College London
Marcelo P Segura Lepe - Bayer Pharma, Berlin, Germany
Paul F O'Reilly - King's College London
Joanne Knight - Lancaster University Ghana
Harold Snieder - University Medical Center Groningen
Norihiro Kato - Gene
Jiang He - Tulane University
E Shyong Tai - National University of Singapore
M Abdullah Said - University Medical Center Groningen
David Porteous - University of Edinburgh
Maris Alver - University of Tartu
Neil Poulter - Imperial College London
Martin Farrall - University of Oxford
Ron T Gansevoort - University Medical Center Groningen
Sandosh Padmanabhan - University of Glasgow
Reedik Mägi - University of Tartu
Alice Stanton - Royal College of Surgeons in Ireland
John Connell - University of Dundee
Stephan J L Bakker - University Medical Center Groningen
Andres Metspalu - University of Tartu
Denis C Shields - University College Dublin
Simon Thom - Imperial College London
Morris Brown - Queen Mary University of London
Peter Sever - Imperial College London
Tõnu Esko - University of Tartu
Caroline Hayward - University of Edinburgh
Pim van der Harst - University Medical Center Groningen
Danish Saleheen - University of Cambridge
Rajiv Chowdhury - University of Cambridge
John C Chambers - Nanyang Technological University
Daniel I Chasman - Harvard Medical School
Aravinda Chakravarti - Johns Hopkins University School of Medicine
Christopher Newton-Cheh - Massachusetts General Hospital
Cecilia M Lindgren - University of Oxford
Daniel Levy - National Heart Lung and Blood Institute
Jaspal S Kooner - Imperial College London
Bernard Keavney - Manchester Academic Health Science Centre
Maciej Tomaszewski - Manchester Academic Health Science Centre
Nilesh J Samani - NIHR Leicester Cardiovascular Biomedical Research Unit
Joanna M M Howson - University of Cambridge
Martin D Tobin - University of Leicester
Patricia B Munroe - Queen Mary University of London
Georg B Ehret - University Hospital of Geneva
Louise V Wain - University of Leicester
International Consortium of Blood Pressure (ICBP) 1000G Analyses
Jaakko Tuomilehto - King Abdulaziz University
Publication Details: Nature genetics, Vol.49(3), pp.403-415
Grant note: Wellcome Trust MR/L01632X/1 / Medical Research Council PG/16/49/32176 / British Heart Foundation RG/15/12/31616 / British Heart Foundation G0800270 / Medical Research Council MC_QA137853 / Medical Research Council MR/N015746/1 / Medical Research Council MR/L01341X/1 / Medical Research Council RG/08/014/24067 / British Heart Foundation SP/13/2/30111 / British Heart Foundation MC_UU_12015/1 / Medical Research Council MR/L003120/1 / Medical Research Council R01 HL124262 / NHLBI NIH HHS MR/K006584/1 / Medical Research Council G0600237 / Medical Research Council R01 HL086694 / NHLBI NIH HHS MR/L016311/1 / Medical Research Council R01 HL113933 / NHLBI NIH HHS R01 HL128782 / NHLBI NIH HHS CZD/16/6/4 / Chief Scientist Office MC_PC_U127561128 / Medical Research Council MR/K026992/1 / Medical Research Council BB/F019394/1 / Biotechnology and Biological Sciences Research Council MC_UU_12013/3 / Medical Research Council 268834 / European Research Council
Identifiers: 9937438808331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article