The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Articolo
Data di Pubblicazione:
2016
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.
Tipologia CRIS:
Articolo su Rivista
Elenco autori:
Ehret, Gb; Ferreira, T; Chasman, Di; Jackson, Au; Schmidt, Em; Johnson, T; Thorleifsson, G; Luan, J; Donnelly, La; Kanoni, S; Petersen, Ak; Pihur, V; Strawbridge, Rj; Shungin, D; Hughes, Mf; Meirelles, O; Kaakinen, M; Bouatia Naji, N; Kristiansson, K; Shah, S; Kleber, Me; Guo, X; Lyytikäinen, Lp; Fava, C; Eriksson, N; Nolte, Im; Magnusson, Pk; Salfati, El; Rallidis, Ls; Theusch, E; Smith, Aj; 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, Is; Cheng, Cy; Chines, Ps; Chung, Rh; Collins, Fs; Connell, Jm; Döring, A; Dallongeville, J; Danesh, J; de Faire, U; Delgado, G; Dominiczak, Af; Doney, As; 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; Franco, Oh; Franco Cereceda, A; Fraser, Rm; Ganesh, Sk; Gao, H; Gertow, K; Gianfagna, Francesco; Gigante, B; Giulianini, F; Goel, A; Goodall, Ah; Goodarzi, Mo; Gorski, M; Gräßler, J; Groves, Cj; Gudnason, V; Gyllensten, U; Hallmans, G; Hartikainen, Al; Hassinen, M; Havulinna, As; Hayward, C; Hercberg, S; Herzig, Kh; Hicks, Aa; Hingorani, Ad; Hirschhorn, Jn; Hofman, A; Holmen, J; Holmen, Ol; Hottenga, Jj; Howard, P; Hsiung, Ca; Hunt, Sc; Ikram, Ma; Illig, T; Iribarren, C; Jensen, Ra; Kähönen, M; Kang, Hm; Kathiresan, S; Keating, Bj; Khaw, Kt; 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, It; Lee, Wj; Levy, D; Li, X; Liang, Kw; 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, Nw; Renström, F; Rettig, R; Rice, Km; Roberts, R; Rose, Lm; Rossouw, J; Samani, Nj; Sanna, S; Saramies, J; Schunkert, H; Sebert, S; Sheu, Wh; Shin, Ya; Sim, X; Smit, Jh; Smith, Av; Sosa, Mx; Spector, Td; Stančáková, A; Stanton, Av; Stirrups, Ke; Stringham, Hm; Sundstrom, J; Swift, Aj; Syvänen, Ac; Tai, Es; 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, Ep; Vasan, Rs; Verwoert, Gc; Virtamo, J; Vitart, V; Voight, Bf; Vollenweider, P; Wagner, A; Wain, Lv; Wareham, Nj; Watkins, H; Weder, Ab; Westra, Hj; Wilks, R; Wilsgaard, T; Wilson, Jf; Wong, Ty; Yang, Tp; Yao, J; Yengo, L; Zhang, W; Zhao, Jh; Zhu, X; Bovet, P; Cooper, Rs; Mohlke, Kl; Saleheen, D; Lee, Jy; 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, Yd; Rotter, Ji; Froguel, P; Jarvelin, Mr; Lakatta, Eg; Kuulasmaa, K; Franks, Pw; Hamsten, A; Wichmann, He; Palmer, Cn; Stefansson, K; Ridker, Pm; Loos, Rj; Chakravarti, A; Deloukas, P; Morris, Ap; Newton Cheh, C; Munroe, Pb
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