The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
2016 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 10, 1171-1184 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2016. Vol. 48, no 10, 1171-1184 p.
IdentifiersURN: urn:nbn:se:uu:diva-306252DOI: 10.1038/ng.3667ISI: 000384391600012PubMedID: 27618452OAI: oai:DiVA.org:uu-306252DiVA: diva2:1040293