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


Authors: 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.; Kaakinen, M.; Bouatia-Naji, N.; Kristiansson, K.; Shah, S; Kleber, M. E.; Guo, X; Lyytikainen, L. P.; Fava, C.; Eriksson, N.; Nolte, I. M.; Magnusson, P. K.; Salfati, E. L.; Rallidis, L. S.; Theusch, E.; Smith, A. J.; Folkersen, L.; Witkowska, K.; Pers, T. H.; Joehanes, R; Kim, S. K.; Lataniotis, L.; Jansen, R.; Johnson, A. D.; Warren, H.; Kim, Y. J.; Zhao, W; Wu, Y; Tayo, B. O.; Bochud, M; CHARGE-EchoGen Consortium; CHARGE-HF Consortium; Wellcome Trust Case Control Consortium; Absher, D.; Adair, L. S.; Amin, N; Arking, D. E.; Axelsson, T.; Baldassarre, D; Balkau, B; Bandinelli, S; Barnes, M. R.; Barroso, I; Bevan, S.; Bis, J. C.; Bjornsdottir, G.; Boehnke, M; Boerwinkle, E; Bonnycastle, L. L.; Boomsma, D. I.; Bornstein, S. R.; Brown, M. J.; Burnier, M.; Cabrera, C. P.; Chambers, J. C.; Chang, I. S.; Cheng, C. Y.; Chines, P. S.; Chung, R. H.; Collins, F. S.; Connell, J. M.; Doring, A.; Dallongeville, J.; Danesh, J; de Faire, U; Delgado, G; Dominiczak, A. F.; Doney, A. S.; Drenos, F.; Edkins, S.; Eicher, J. D.; Elosua, R.; Enroth, S; Erdmann, J.; Eriksson, P.; Esko, T; Evangelou, E; Evans, A; Fall, T.; Farrall, M; Felix, J. F.; Ferrieres, J.; Ferrucci, L; Fornage, M; Forrester, T; Franceschini, N; Franco, O. H.; Franco-Cereceda, A.; Fraser, R. M.; Ganesh, S. K.; Gao, H; Gertow, K; Gianfagna, F.; Gigante, B; Giulianini, F; Goel, A; Goodall, A. H.; Goodarzi, M. O.; Gorski, M; Grassler, J.; Groves, C. J.; Gudnason, V; Gyllensten, U; Hallmans, G; Hartikainen, A. L.; Hassinen, M; Havulinna, A. S.; Hayward, C; Hercberg, S.; Herzig, K. H.; Hicks, A. A.; Hingorani, A. D.; Hirschhorn, J. N.; Hofman, A; Holmen, J.; Holmen, O. L.; Hottenga, J. J.; Howard, P.; Hsiung, C. A.; Hunt, S. C.; Ikram, M. A.; Illig, T; Iribarren, C.; Jensen, R. A.; Kahonen, M.; Kang, H. M.; Kathiresan, S.; Keating, B. J.; Khaw, K. T.; Kim, Y. K.; Kim, E; Kivimaki, M; Klopp, N.; Kolovou, G; Komulainen, P; Kooner, J. S.; Kosova, G.; Krauss, R. M.; Kuh, D; Kutalik, Z; Kuusisto, J; Kvaloy, K.; Lakka, T. A.; Lee, N. R.; Lee, I. T.; Lee, W. J.; Levy, D; Li, X; Liang, K. W.; Lin, H; Lin, L.; Lindstrom, J.; Lobbens, S; Mannisto, S.; Muller, G.; Muller-Nurasyid, M.; Mach, F.; Markus, H. S.; Marouli, E; McCarthy, M. I.; McKenzie, C. A.; Meneton, P.; Menni, C; Metspalu, A; Mijatovic, V; Moilanen, L.; Montasser, M. E.; Morris, A. D.; Morrison, A. C.; Mulas, A.; Nagaraja, R.; Narisu, N; Nikus, K; O'Donnell, C. J.; O'Reilly, P. F.; Ong, K. K.; Paccaud, F.; Palmer, C. D.; Parsa, A; Pedersen, N. L.; Penninx, B. W.; Perola, M; Peters, A; Poulter, N; Pramstaller, P. P.; Psaty, B. M.; Quertermous, T.; Rao, D. C.; Rasheed, A.; Rayner, N. W.; Renstrom, F.; Rettig, R; Rice, K. M.; Roberts, R.; Rose, L. M.; Rossouw, J.; Samani, N. J.; Sanna, S; Saramies, J.; Schunkert, H.; Sebert, S.; Sheu, W. H.; Shin, Y. A.; Sim, X; Smit, J. H.; Smith, A. V.; Sosa, M. X.; Spector, T. D.; Stancakova, A.; Stanton, A. V.; Stirrups, K. E.; Stringham, H. M.; Sundstrom, J.; Swift, A. J.; Syvanen, A. C.; Tai, E. S.; Tanaka, T; Tarasov, K. V.; Teumer, A; Thorsteinsdottir, U; Tobin, M. D.; Tremoli, E; Uitterlinden, A. G.; Uusitupa, M.; Vaez, A.; Vaidya, D; van Duijn, C. M.; van Iperen, E. P.; Vasan, R. S.; Verwoert, G. C.; Virtamo, J.; Vitart, V; Voight, B. F.; Vollenweider, P; Wagner, A.; Wain, L. V.; Wareham, N. J.; Watkins, H; Weder, A. B.; Westra, H. J.; Wilks, R.; Wilsgaard, T.; Wilson, J. F.; Wong, T. Y.; Yang, T. P.; Yao, J; Yengo, L; Zhang, W; Zhao, J. H.; Zhu, X; Bovet, P; Cooper, R. S.; Mohlke, K. L.; Saleheen, D.; Lee, J. Y.; Elliott, P; Gierman, H. J.; Willer, C. J.; Franke, L.; Hovingh, G. K.; Taylor, K. D.; Dedoussis, G; Sever, P; Wong, A; Lind, L; Assimes, T. L.; Njolstad, I.; Schwarz, P. E.; Langenberg, C; Snieder, H; Caulfield, M. J.; Melander, O; Laakso, M; Saltevo, J.; Rauramaa, R; Tuomilehto, J; Ingelsson, E; Lehtimaki, T.; Hveem, K; Palmas, W; Marz, W.; Kumari, M; Salomaa, V; Chen, Y. D.; Rotter, J. I.; Froguel, P; Jarvelin, M. R.; Lakatta, E. G.; Kuulasmaa, K.; Franks, P. W.; Hamsten, A; Wichmann, H. E.; Palmer, C. N.; Stefansson, K; Ridker, P. M.; Loos, R. J.; Chakravarti, A; Deloukas, P; Morris, A. P.; Newton-Cheh, C.; Munroe, P. B.
Article Title: The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
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.
Journal Title: Nature genetics
Volume: 48
Issue: 10
ISSN: 1061-4036; 1061-4036
Publisher: Unknown  
Journal Place: United States
Date Published: 2016
Start Page: 1171
End Page: 1184
Language: ENG
DOI/URL:
Notes: LR: 20161019; GR: R01 HL086694/HL/NHLBI NIH HHS/United States; GR: R01 HL113933/HL/NHLBI NIH HHS/United States; JID: 9216904; NIHMS810971; PMCR: 2017/03/12; 2015/07/09 [received]; 2016/08/15 [accepted]; ppublish