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

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.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., Doring, 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., 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.-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.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., Njolstad, I., Schwarz, P.E.H., 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.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. and Munroe, P.B. (2016) The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals. Nature Genetics, 48 10: 1171-1184. doi:10.1038/ng.3667


Author 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.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.
Doring, 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.
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.-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.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.
Njolstad, I.
Schwarz, P.E.H.
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.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.
Title The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
1061-4036
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1038/ng.3667
Open Access Status Not yet assessed
Volume 48
Issue 10
Start page 1171
End page 1184
Total pages 14
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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