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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Wain, LV; Vaez, A; Jansen, R; Joehanes, R; van der Most, PJ; Erzurumluoglu, AM; O'Reilly, PF; Cabrera, CP; Warren, HR; Rose, LM; et al. Wain, LV; Vaez, A; Jansen, R; Joehanes, R; van der Most, PJ; Erzurumluoglu, AM; O'Reilly, PF; Cabrera, CP; Warren, HR; Rose, LM; Verwoert, GC; Hottenga, J-J; Strawbridge, RJ; Esko, T; Arking, DE; Hwang, S-J; Guo, X; Kutalik, Z; Trompet, S; Shrine, N; Teumer, A; Ried, JS; Bis, JC; Smith, AV; Amin, N; Nolte, IM; Lyytikäinen, L-P; Mahajan, A; Wareham, NJ; Hofer, E; Joshi, PK; Kristiansson, K; Traglia, M; Havulinna, AS; Goel, A; Nalls, MA; Sõber, S; Vuckovic, D; Luan, J; Del Greco M, F; Ayers, KL; Marrugat, J; Ruggiero, D; Lopez, LM; Niiranen, T; Enroth, S; Jackson, AU; Nelson, CP; Huffman, JE; Zhang, W; Marten, J; Gandin, I; Harris, SE; Zemunik, T; Lu, Y; Evangelou, E; Shah, N; de Borst, MH; Mangino, M; Prins, BP; Campbell, A; Li-Gao, R; Chauhan, G; Oldmeadow, C; Abecasis, G; Abedi, M; Barbieri, CM; Barnes, MR; Batini, C; Beilby, J; Blake, T; Boehnke, M; Bottinger, EP; Braund, PS; Brown, M; Brumat, M; Campbell, H; Chambers, JC; Cocca, M; Collins, F; Connell, J; Cordell, HJ; Damman, JJ; Davies, G; de Geus, EJ; de Mutsert, R; Deelen, J; Demirkale, Y; Doney, ASF; Dörr, M; Farrall, M; Ferreira, T; Frånberg, M; Gao, H; Giedraitis, V; Gieger, C; Giulianini, F; Gow, AJ; Hamsten, A; Harris, TB; Hofman, A; Holliday, EG; Hui, J; Jarvelin, M-R; Johansson, Å; Johnson, AD; Jousilahti, P; Jula, A; Kähönen, M; Kathiresan, S; Khaw, K-T; Kolcic, I; Koskinen, S; Langenberg, C; Larson, M; Launer, LJ; Lehne, B; Liewald, DCM; Lin, L; Lind, L; Mach, F; Mamasoula, C; Menni, C; Mifsud, B; Milaneschi, Y; Morgan, A; Morris, AD; Morrison, AC; Munson, PJ; Nandakumar, P; Nguyen, QT; Nutile, T; Oldehinkel, AJ; Oostra, BA; Org, E; Padmanabhan, S; Palotie, A; Paré, G; Pattie, A; Penninx, BWJH; Poulter, N; Pramstaller, PP; Raitakari, OT; Ren, M; Rice, K; Ridker, PM; Riese, H; Ripatti, S; Robino, A; Rotter, JI; Rudan, I; Saba, Y; Saint Pierre, A; Sala, CF; Sarin, A-P; Schmidt, R; Scott, R; Seelen, MA; Shields, DC; Siscovick, D; Sorice, R; Stanton, A; Stott, DJ; Sundström, J; Swertz, M; Taylor, KD; Thom, S; Tzoulaki, I; Tzourio, C; Uitterlinden, AG; Völker, U; Vollenweider, P; Wild, S; Willemsen, G; Wright, AF; Yao, J; Thériault, S; Conen, D; Attia, J; Sever, P; Debette, S; Mook-Kanamori, DO; Zeggini, E; Spector, TD; van der Harst, P; Palmer, CNA; Vergnaud, A-C; Loos, RJF; Polasek, O; Starr, JM; Girotto, G; Hayward, C; Kooner, JS; Lindgren, CM; Vitart, V; Samani, NJ; Tuomilehto, J; Gyllensten, U; Knekt, P; Deary, IJ; Ciullo, M; Elosua, R; Keavney, BD; Hicks, AA; Scott, RA; Gasparini, P; Laan, M; Liu, Y; Watkins, H; Hartman, CA; Salomaa, V; Toniolo, D; Perola, M; Wilson, JF; Schmidt, H; Zhao, JH; Lehtimäki, T; van Duijn, CM; Gudnason, V; Psaty, BM; Peters, A; Rettig, R; James, A; Jukema, JW; Strachan, DP; Palmas, W; Metspalu, A; Ingelsson, E; Boomsma, DI; Franco, OH; Bochud, M; Newton-Cheh, C; Munroe, PB; Elliott, P; Chasman, DI; Chakravarti, A; Knight, J; Morris, AP; Levy, D; Tobin, MD; Snieder, H; Caulfield, MJ; Ehret, GB (2017) Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney. Hypertension, 70 (3). e4-e19. ISSN 1524-4563 https://doi.org/10.1161/HYPERTENSIONAHA.117.09438
SGUL Authors: Strachan, David Peter

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Abstract

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Item Type: Article
Additional Information: This is a non-final version of an article published in final form in Wain, LV; Vaez, A; Jansen, R; Joehanes, R; van der Most, PJ; Erzurumluoglu, AM; O'Reilly, PF; Cabrera, CP; Warren, HR; Rose, LM; et al. (2017) Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney. Hypertension. Vol. 70 no. 3 e4-e19.
Keywords: GWAS, blood pressure, cardiovascular risk, complex traits, eSNP, hypertension, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Hypertension
ISSN: 1524-4563
Language: eng
Dates:
DateEvent
September 2017Published
24 July 2017Published Online
30 June 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
G9521010DMedical Research Councilhttp://dx.doi.org/10.13039/501100000265
PG/02/128British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
G0000934Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
068545/Z/02Wellcome Trusthttp://dx.doi.org/10.13039/100004440
076113/B/04/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
079895Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MC_U106179471Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12015/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
104036/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
072960/Z/03/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
084726/Z/08/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
084727/Z/08/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
085475/Z/08/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
085475/B/08/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
BHF/RG/2000004British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
SP/04/002British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
G060196Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G070093Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
084723/Z/08/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
WT098017Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT090532Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT064890Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT098017Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT090532Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 28739976
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/109019
Publisher's version: https://doi.org/10.1161/HYPERTENSIONAHA.117.09438

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