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

CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium

Research output: Contribution to journalArticlepeer-review

323 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1171-84
Number of pages14
JournalNature Genetics
Volume48
Issue number10
Early online date12 Sept 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Journal Article

Fingerprint

Dive into the research topics of 'The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals'. Together they form a unique fingerprint.

Cite this