The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Research output: Contribution to journal › Journal article › Research › peer-review
Georg B Ehret, Teresa Ferreira, Daniel I Chasman, Anne U Jackson, Ellen M Schmidt, Toby Johnson, Gudmar Thorleifsson, Jian'an Luan, Louise A Donnelly, Stavroula Kanoni, Ann-Kristin Petersen, Vasyl Pihur, Rona J Strawbridge, Dmitry Shungin, Maria F Hughes, Osorio Meirelles, Marika Kaakinen, Nabila Bouatia-Naji, Kati Kristiansson, Sonia Shah & 31 others
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.
|Number of pages||14|
|Publication status||Published - 12 Sep 2016|