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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 publication

DOI

10.1038/ng.3667

Type

Journal article

Journal

Nat Genet

Publication Date

10/2016

Volume

48

Pages

1171 - 1184

Keywords

African Continental Ancestry Group, Asian Continental Ancestry Group, Blood Pressure, Cells, Cultured, Genome-Wide Association Study, Humans, Hypertension, Microarray Analysis, Polymorphism, Single Nucleotide