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

Int Consortium Blood Pressure ICBP, CHD Exome Consortium, ExomeBP Consortium, T2D-GENES Consortium, GoT2D Genes Consortium, CHARGE BP Exome Consortium, iGEN-BP Consortium, UK Biobank CardioMetab Consortium, BIOS Consortium, Lifelines Cohort Study, Understanding Soc Sci Grp, Helen R. Warren, Evangelos Evangelou, Claudia P. Cabrera, He Gao, Meixia Ren, Borbala Mifsud, Ioanna Ntalla, Praveen Surendran, Chunyu LiuJames 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 Magi, Caroline Hayward, Peter K. Joshi, Lorna M. Lopez, Jonathan Marten, Sarah E. Harris, Archie Campbell, Harry Campbell, Gail Davies, Alan J. Gow, David C. M. Liewald, Andrew D. Morris, Alison Pattie, Igor Rudan, Alan F. Wright, John M. Starr, Caroline Hayward, Veronique Vitart, Ian J. Deary, James F. Wilson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)403-415
Number of pages13
JournalNature Genetics
Volume49
Issue number3
Early online date30 Jan 2017
DOIs
Publication statusPublished - Mar 2017

Keywords

  • CORONARY-ARTERY-DISEASE
  • ENDOTHELIAL-CELL
  • MYOCARDIAL-INFARCTION
  • NEUROTROPHIC FACTOR
  • NADPH OXIDASE
  • UK BIOBANK
  • KEY ROLE
  • IN-VIVO
  • HYPERTENSION
  • COMMON

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