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

Nat Genet
Authors
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.

Year of Publication
2016
Journal
Nat Genet
Volume
48
Issue
10
Pages
1171-84
Date Published
2016 Oct
ISSN
1546-1718
DOI
10.1038/ng.3667
PubMed ID
27618452
PubMed Central ID
PMC5042863
Links
Grant list
R01 HL086694 / HL / NHLBI NIH HHS / United States
MR/L01341X/1 / Medical Research Council / United Kingdom
R01 AG025941 / AG / NIA NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL113933 / HL / NHLBI NIH HHS / United States