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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ehret, GB; Ferreira, T; Chasman, DI; Jackson, AU; Schmidt, EM; Johnson, T; Thorleifsson, G; Luan, J; Donnelly, LA; Kanoni, S; Petersen, A-K; Pihur, V; Strawbridge, RJ; Shungin, D; Hughes, MF; Meirelles, O; Kaakinen, M; Bouatia-Naji, N; Kristiansson, K; Shah, S; Kleber, ME; Guo, X; Lyytikäinen, L-P; Fava, C; Eriksson, N; Nolte, IM; Magnusson, PK; Salfati, EL; Rallidis, LS; Theusch, E; Smith, AJP; Folkersen, L; Witkowska, K; Pers, TH; Joehanes, R; Kim, SK; Lataniotis, L; Jansen, R; Johnson, AD; Warren, H; Kim, YJ; Zhao, W; Wu, Y; Tayo, BO; Bochud, M; CHARGE-EchoGen consortium, ; CHARGE-HF consortium, ; Wellcome Trust Case Control Consortium, ; Absher, D; Adair, LS; Amin, N; Arking, DE; Axelsson, T; Baldassarre, D; Balkau, B; Bandinelli, S; Barnes, MR; Barroso, I; Bevan, S; Bis, JC; Bjornsdottir, G; Boehnke, M; Boerwinkle, E; Bonnycastle, LL; Boomsma, DI; Bornstein, SR; Brown, MJ; Burnier, M; Cabrera, CP; Chambers, JC; Chang, I-S; Cheng, C-Y; Chines, PS; Chung, R-H; Collins, FS; Connell, JM; Döring, A; Dallongeville, J; Danesh, J; de Faire, U; Delgado, G; Dominiczak, AF; Doney, ASF; Drenos, F; Edkins, S; Eicher, JD; Elosua, R; Enroth, S; Erdmann, J; Eriksson, P; Esko, T; Evangelou, E; Evans, A; Fall, T; Farrall, M; Felix, JF; Ferrières, J; Ferrucci, L; Fornage, M; Forrester, T; Franceschini, N; Duran, OHF; Franco-Cereceda, A; Fraser, RM; Ganesh, SK; Gao, H; Gertow, K; Gianfagna, F; Gigante, B; Giulianini, F; Goel, A; Goodall, AH; Goodarzi, MO; Gorski, M; Gräßler, J; Groves, C; Gudnason, V; Gyllensten, U; Hallmans, G; Hartikainen, A-L; Hassinen, M; Havulinna, AS; Hayward, C; Hercberg, S; Herzig, K-H; Hicks, AA; Hingorani, AD; Hirschhorn, JN; Hofman, A; Holmen, J; Holmen, OL; Hottenga, J-J; Howard, P; Hsiung, CA; Hunt, SC; Ikram, MA; Illig, T; Iribarren, C; Jensen, RA; Kähönen, M; Kang, H; Kathiresan, S; Keating, BJ; Khaw, K-T; Kim, YK; Kim, E; Kivimaki, M; Klopp, N; Kolovou, G; Komulainen, P; Kooner, JS; Kosova, G; Krauss, RM; Kuh, D; Kutalik, Z; Kuusisto, J; Kvaløy, K; Lakka, TA; Lee, NR; Lee, I-T; Lee, W-J; Levy, D; Li, X; Liang, K-W; Lin, H; Lin, L; Lindström, J; Lobbens, S; Männistö, S; Müller, G; Müller-Nurasyid, M; Mach, F; Markus, HS; Marouli, E; McCarthy, MI; McKenzie, CA; Meneton, P; Menni, C; Metspalu, A; Mijatovic, V; Moilanen, L; Montasser, ME; Morris, AD; Morrison, AC; Mulas, A; Nagaraja, R; Narisu, N; Nikus, K; O'Donnell, CJ; O'Reilly, PF; Ong, KK; Paccaud, F; Palmer, CD; Parsa, A; Pedersen, NL; Penninx, BW; Perola, M; Peters, A; Poulter, N; Pramstaller, PP; Psaty, BM; Quertermous, T; Rao, DC; Rasheed, A; Rayner, NWNWR; Renström, F; Rettig, R; Rice, KM; Roberts, R; Rose, LM; Rossouw, J; Samani, NJ; Sanna, S; Saramies, J; Schunkert, H; Sebert, S; Sheu, WH-H; Shin, Y-A; Sim, X; Smit, JH; Smith, AV; Sosa, MX; Spector, TD; StanĨáková, A; Stanton, A; Stirrups, KE; Stringham, HM; Sundstrom, J; Swift, AJ; Syvänen, A-C; Tai, E-S; Tanaka, T; Tarasov, KV; Teumer, A; Thorsteinsdottir, U; Tobin, MD; Tremoli, E; Uitterlinden, AG; Uusitupa, M; Vaez, A; Vaidya, D; van Duijn, CM; van Iperen, EPA; Vasan, RS; Verwoert, GC; Virtamo, J; Vitart, V; Voight, BF; Vollenweider, P; Wagner, A; Wain, LV; Wareham, NJ; Watkins, H; Weder, AB; Westra, H-J; Wilks, R; Wilsgaard, T; Wilson, JF; Wong, TY; Yang, T-P; Yao, J; Yengo, L; Zhang, W; Zhao, JH; Zhu, X; Bovet, P; Cooper, RS; Mohlke, KL; Saleheen, D; Lee, J-Y; Elliott, P; Gierman, HJ; Willer, CJ; Franke, L; Hovingh, GK; Taylor, KD; Dedoussis, G; Sever, P; Wong, A; Lind, L; Assimes, TL; Njølstad, I; Schwarz, PE; Langenberg, C; Snieder, H; Caulfield, MJ; Melander, O; Laakso, M; Saltevo, J; Rauramaa, R; Tuomilehto, J; Ingelsson, E; Lehtimäki, T; Hveem, K; Palmas, W; März, W; Kumari, M; Salomaa, V; Chen, Y-DI; Rotter, JI; Froguel, P; Jarvelin, M-R; Lakatta, EG; Kuulasmaa, K; Franks, PW; Hamsten, A; Wichmann, H-E; Palmer, CNA; Stefansson, K; Ridker, PM; Loos, RJF; Chakravarti, A; Deloukas, P; Morris, AP; Newton-Cheh, C; Munroe, PB

Published Date

  • October 2016

Published In

Volume / Issue

  • 48 / 10

Start / End Page

  • 1171 - 1184

PubMed ID

  • 27618452

Pubmed Central ID

  • 27618452

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.3667

Language

  • eng