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

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3085504 70 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2016 Nature America, Inc. All rights reserved.
Έτος δημοσίευσης:
2016
Συγγραφείς:
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.
Lyytikäinen, L.-P.
Fava, C.
Eriksson, N.
Nolte, I.M.
Magnusson, P.K.
Salfati, E.L.
Rallidis, L.S.
Theusch, E.
Smith, A.J.P.
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.
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.
Döring, A.
Dallongeville, J.
Danesh, J.
De Faire, U.
Delgado, G.
Dominiczak, A.F.
Doney, A.S.F.
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.
Ferrières, 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.
Gräßler, 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.
Kähönen, 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.
Kvaløy, K.
Lakka, T.A.
Lee, N.R.
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, 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.
Renström, 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.-H.
Shin, Y.-A.
Sim, X.
Smit, J.H.
Smith, A.V.
Sosa, M.X.
Spector, T.D.
Stančáková, A.
Stanton, A.V.
Stirrups, K.E.
Stringham, H.M.
Sundstrom, J.
Swift, A.J.
Syvänen, 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.A.
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.
Njølstad, I.
Schwarz, P.E.H.
Langenberg, C.
Snieder, H.
Caulfield, M.J.
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.-D.I.
Rotter, J.I.
Froguel, P.
Jarvelin, M.-R.
Lakatta, E.G.
Kuulasmaa, K.
Franks, P.W.
Hamsten, A.
Wichmann, H.-E.
Palmer, C.N.A.
Stefansson, K.
Ridker, P.M.
Loos, R.J.F.
Chakravarti, A.
Deloukas, P.
Morris, A.P.
Newton-Cheh, C.
Munroe, P.B.
Περιοδικό:
Nature Genetics
Εκδότης:
Nature Publishing Group
Τόμος:
48
Αριθμός / τεύχος:
10
Σελίδες:
1171-1184
Λέξεις-κλειδιά:
Article; Asian; Black person; blood pressure regulation; blood vessel tone; cardiovascular risk; diastolic blood pressure; gene frequency; gene locus; genetic association; genetic heterogeneity; genetic variability; genome-wide association study; genotype; human; human cell; meta analysis (topic); priority journal; single nucleotide polymorphism; systolic blood pressure; target organ; validation study; vascular endothelial cell; Asian continental ancestry group; blood pressure; cell culture; genetics; hypertension; meta analysis; microarray analysis; pathology, African Continental Ancestry Group; Asian Continental Ancestry Group; Blood Pressure; Cells, Cultured; Genome-Wide Association Study; Humans; Hypertension; Microarray Analysis; Polymorphism, Single Nucleotide
Επίσημο URL (Εκδότης):
DOI:
10.1038/ng.3667
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