The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Archive ouverte
Ehret, Georg B. | Ferreira, Teresa | Chasman, Daniel I. | Jackson, Anne U. | Schmidt, Ellen M. | Johnson, Toby | Thorleifsson, Gudmar | Luan, Jian'An | Donnelly, Louise A. | Kanoni, Stavroula | Petersen, Ann -Kristin | Pihurl, Vasyl | Strawbridge, Rona J. | Shungin, Dmitry | Hughes, Maria F. | Meirelles, Osorio | Kaakinen, Marika | Bouatia-Naji, Nabila | Kristiansson, Kati | Shah, Sonia | Kleber, Marcus E. | Guo, Xiuqing | Lyytikäinen, Leo-Pekka | Fava, Cristiano | Eriksson, Nidas | Nolte, Ilja M. | Magnusson, Patrik K. | Salfati, Elias L. | Rallidis, Loukianos S. | Theusch, Elizabeth | Smith, Andrew J. P. | Folkersen, Lasse | Witkowska, Kate | Pers, Tune H. | Joehanes, Roby | Kim, Stuart K. | Lataniotis, Lazaros | Jansen, Rick | Johnson, Andrew D. | Warren, Helen | Kim, Young Jin | Zhao, Wei | Wu, Ying | Tayo, Bamidele O. | Bochud, Murielle | Absher, Devin | Adair, Linda S. | Amin, Najaf | Arkingl, Dan E. | Axelsson, Tomas | Baldassarre, Damian | Balkau, Beverley | Bandinelli, Stefania | Barnes, Michael R. | Barroso, Inês | Bevan, Stephen | Bis, Joshua C. | Bjornsdottir, Gyda | Boehnke, Michael | Boerwinkle, Eric | Bonnycastle, Lori L. | Boomsma, Dorret I. | Bornstein, Stefan R. | Brown, Morris J. | Burnier, Michel | Cabrera, Claudia P. | Chambers, John C. | Chang, I-Shou | Cheng, Ching-Yu | Chines, Peter S. | Chung, Ren-Hua | Collins, Francis S. | Connell, John M. | Döring, Angela | Dallongeville, Jean | Danesh, John | de Faire, Ulf | Delgado, Graciela | Dominiczak, Anna F. | Doney, Alex S. F. | Drenos, Fotios | Edkins, Sarah | Eicher, John D. | Elosua, Roberto | Enroth, Stefan | Erdmann, Jeanette | Eriksson, Per | Esko, Tonu | Evangelou, Evangelos | Evans, Alun | Fai, Tove | Farrall, Martin | Felixl, Janine F. | Ferrières, Jean | Ferrucci, Luigi | Fornage, Myriam | Forrester, Terrence | Franceschinil, Nora | Franco, Oscar H. | Franco-Cereceda, Anders | Fraser, Ross M. | Hercberg, Serge | Meneton, Pierre
Edité par
CCSD ; Nature Publishing Group -
International audience.
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.
