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

Nat Genet. 2016 Oct;48(10):1171-1184. doi: 10.1038/ng.3667. Epub 2016 Sep 12.


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.

Publication types

  • Meta-Analysis

MeSH terms

  • Asian People / genetics
  • Black People / genetics
  • Blood Pressure / genetics*
  • Cells, Cultured
  • Genome-Wide Association Study
  • Humans
  • Hypertension / genetics
  • Hypertension / pathology
  • Microarray Analysis
  • Polymorphism, Single Nucleotide

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