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.; Lyytikäinen, L.P.; Fava, C.; Eriksson, N.; Nolte, I.M.; Magnusson, P.K.; Salfati, E.L.; Rallidis, L.S.; Theusch, E.; Smith, A.J.; 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.; 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.; 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.; 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.; 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.; Rotter, J.I.; Froguel, P.; Jarvelin, M.R.; Lakatta, E.G.; Kuulasmaa, K.; Franks, P.W.; Hamsten, A.; Wichmann, H.E.; Palmer, C.N.; Stefansson, K.; Ridker, P.M.; Loos, R.J.; Chakravarti, A.; Deloukas, P.; Morris, A.P.; Newton-Cheh, C.; Munroe, P.B.

doi:10.1038/ng.3667

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

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Serval ID

serval:BIB_C3107C8B0FD2

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature genetics

Author(s)

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., 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., 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., 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., 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., 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., Rotter J.I., Froguel P., Jarvelin M.R., Lakatta E.G., Kuulasmaa K., Franks P.W., Hamsten A., Wichmann H.E., Palmer C.N., Stefansson K., Ridker P.M., Loos R.J., Chakravarti A., Deloukas P., Morris A.P., Newton-Cheh C., Munroe P.B.

Working group(s)

CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

10/2016

Peer-reviewed

Oui

Volume

Number

Pages

1171-1184

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis
Publication Status: ppublish

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.

Keywords

African Continental Ancestry Group/genetics, Asian Continental Ancestry Group/genetics, Blood Pressure/genetics, Cells, Cultured, Genome-Wide Association Study, Humans, Hypertension/genetics, Hypertension/pathology, Microarray Analysis, Polymorphism, Single Nucleotide

URN

urn:nbn:ch:serval-BIB_C3107C8B0FD22

OAI-PMH

oai:serval.unil.ch:BIB_C3107C8B0FD2

DOI

10.1038/ng.3667

Pubmed

27618452

Web of science

000384391600012

Create date

29/09/2016 15:59