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

TitreThe genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.
Publication TypeJournal Article
Year of Publication2016
AuthorsEhret, GB, Ferreira, T, Chasman, DI, Jackson, AU, Schmidt, EM, Johnson, T, Thorleifsson, G, Luan, J'an, 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, Lyytikainen, 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, YJin, Zhao, W, Wu, Y, Tayo, BO, Bochud, M, 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, Ferrieres, J, Ferrucci, L, Fornage, M, Forrester, T, Franceschini, N, Franco, OH, 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, CJ, 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, OLingaas, Hottenga, J-J, Howard, P, Hsiung, CA, Hunt, SC, M Ikram, A, Illig, T, Iribarren, C, Jensen, RA, Kahonen, M, Kang, HMin, Kathiresan, S, Keating, BJ, Khaw, K-T, Kim, YKyoung, 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, Muller, 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, N Rayner, W, Renstrom, 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, Stancakova, A, Stanton, AV, Stirrups, KE, Stringham, HM, Sundström, 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, JHua, Zhu, X, Bovet, P, Cooper, RS, Mohlke, KL, Saleheen, D, Lee, J-Y, Elliott, P, Gierman, HJ, Willer, CJ, Franke, L, G Hovingh, K, Taylor, KD, Dedoussis, G, Sever, P, Wong, A, Lind, L, Assimes, TL, Njølstad, I, Schwarz, PEH, Langenberg, C, Snieder, H, Caulfield, MJ, Melander, O, Laakso, M, Saltevo, J, Rauramaa, R, Tuomilehto, J, Ingelsson, E, Lehtimaki, T, Hveem, K, Palmas, W, März, W, Kumari, M, Salomaa, V, Chen, Y-derI, 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
Corporate AuthorsCHARGE-EchoGen Consortium, CHARGE-HF consortium, Consortium, WTrust Case
JournalNature Genetics
Volume48
Issue10
Pagination1171-84
Date Published10/2016
DOI10.1038/ng.3667
ISSN1546-1718
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.

Alternate URL

http://www.ncbi.nlm.nih.gov/pubmed/27618452?dopt=Abstract

First publication date (online)

09/2016

Alternate JournalNat. Genet.
Citation Key / SERVAL ID7698
Peer reviewRefereed
PubMed ID27618452
PubMed Central IDPMC5042863
Grant ListRG/13/2/30098 / / British Heart Foundation / United Kingdom
R01 HL122684 / HL / NHLBI NIH HHS / United States
R01 DK072193 / DK / NIDDK NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
MC_UU_12019/1 / / Medical Research Council / United Kingdom
G1000143 / / Medical Research Council / United Kingdom
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/L01341X/1 / / Medical Research Council / United Kingdom
R01 AG025941 / AG / NIA NIH HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
T32 HL007208 / HL / NHLBI NIH HHS / United States
T32 HL098049 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
G0401527 / / Medical Research Council / United Kingdom
MC_PC_U127561128 / / Medical Research Council / United Kingdom
U01 DK062370 / DK / NIDDK NIH HHS / United States
MR/K006584/1 / / Medical Research Council / United Kingdom
MR/K013351/1 / / Medical Research Council / United Kingdom
RG/14/5/30893 / / British Heart Foundation / United Kingdom
P2C HD050924 / HD / NICHD NIH HHS / United States
R01 HL113933 / HL / NHLBI NIH HHS / United States
G0601261 / / Medical Research Council / United Kingdom
G0600237 / / Medical Research Council / United Kingdom
MC_UU_12013/5 / / Medical Research Council / United Kingdom
RG/10/12/28456 / / British Heart Foundation / United Kingdom
                         

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