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

Research output: Contribution to journalJournal articlepeer-review

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  • 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
  • International Consortium of Blood Pressure (ICBP) 1000G Analyses
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<mark>Journal publication date</mark>20/02/2017
<mark>Journal</mark>Nature Genetics
Volume49
Number of pages13
Pages (from-to)403-415
Publication StatusPublished
Early online date30/01/17
<mark>Original language</mark>English

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.

Bibliographic note

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.