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

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 ShahMarcus E Kleber, Xiuqing Guo, Leo-Pekka Lyytikäinen, Cristiano Fava, Niclas Eriksson, Ilja M Nolte, Patrik K Magnusson, Elias L Salfati, Loukianos S Rallidis, Elizabeth Theusch, Andrew J P Smith, Lasse Folkersen, Kate Witkowska, Tune H Pers, Roby Joehanes, Fotios Drenos, John D Eicher, Alun Evans, Steven C Hunt, Yun Kyoung Kim, Mika Kivimaki, Diana Kuh, Li Lin, Martin D Tobin, Louise V Wain, James F Wilson, Richard S Cooper, Andrew Wong, Meena Kumari, Colin N A Palmer, CHARGE-EchoGen Consortium

Research output: Contribution to journalArticle (Academic Journal)peer-review

202 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)1171-1184
Number of pages14
JournalNature Genetics
Volume48
Issue number10
Early online date12 Sep 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Genome-wide association studies
  • Hypertension

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