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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

Lookup NU author(s): Professor Heather Cordell, Valentina Mamasoula

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Abstract

© 2017 American Heart Association, Inc. 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.


Publication metadata

Author(s): 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, Lyytikainen L-P, Mahajan A, Wareham NJ, Hofer E, Joshi PK, Kristiansson K, Traglia M, Havulinna AS, Goel A, Nalls MA, Sober S, Vuckovic D, Luan J, Del Greco FM, 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, Dorr M, Farrall M, Ferreira T, Franberg 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 A, Johnson AD, Jousilahti P, Jula A, Kahonen 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, Pare 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, Sundstrom J, Swertz M, Taylor KD, Thom S, Tzoulaki I, Tzourio C, Uitterlinden AG, Volker U, Vollenweider P, Wild S, Willemsen G, Wright AF, Yao J, Theriault 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, Lehtimaki 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

Publication type: Article

Publication status: Published

Journal: Hypertension

Year: 2017

Volume: 70

Issue: 3

Pages: e4-e19

Print publication date: 01/09/2017

Online publication date: 24/07/2017

Acceptance date: 30/06/2017

ISSN (print): 0194-911X

ISSN (electronic): 1524-4563

Publisher: Lippincott Williams and Wilkins

URL: https://doi.org/10.1161/HYPERTENSIONAHA.117.09438

DOI: 10.1161/HYPERTENSIONAHA.117.09438


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