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

CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium, 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 KaakinenNabila Bouatia-Naji, Kati Kristiansson, Sonia Shah, Marcus 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, Stuart K. Kim, Lazaros Lataniotis, Rick Jansen, Andrew D. Johnson, Helen Warren, Young Jin Kim, Wei Zhao, Ying Wu, Bamidele O. Tayo, Murielle Bochud, Devin Absher, John M. Connell, Alex S. F. Doney, Andrew D. Morris, Colin N. A. Palmer, Christopher Newton-Cheh, Patricia B. Munroe

Research output: Contribution to journalArticle

162 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 pages16
JournalNature Genetics
Volume48
Early online date12 Sep 2016
DOIs
Publication statusPublished - Oct 2016

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Keywords

  • Genome-wide association studies
  • Hypertension

Cite this

CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium, Ehret, G. B., Ferreira, T., Chasman, D. I., Jackson, A. U., Schmidt, E. M., Johnson, T., Thorleifsson, G., Luan, J., Donnelly, L. A., Kanoni, S., Petersen, A-K., Pihur, V., Strawbridge, R. J., Shungin, D., Hughes, M. F., Meirelles, O., ... Munroe, P. B. (2016). The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics, 48, 1171-1184. https://doi.org/10.1038/ng.3667