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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Ehret, GB; Ferreira, T; Hassinen, M; Havulinna, AS; Hayward, C; Hercberg, S; Herzig, K-H; ... Munroe, PB; + view all (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics , 48 (10) pp. 1171-1184. 10.1038/ng.3667. Green open access

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Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

Type: Article
Title: The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ng.3667
Publisher version: http://dx.doi.org/10.1038/ng.3667
Language: English
Additional information: Copyright © 2016 Nature America, Inc. All rights reserved.
Keywords: Genome-wide association studies, Hypertension
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery.ucl.ac.uk/id/eprint/1516796
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