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Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Lookup NU author(s): Professor Bernard Keavney, Dr Kristin Ayers, Professor Heather Cordell, Dr Lenore Launer, Valentina Mamasoula

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Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.


Publication metadata

Author(s): Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, Ntalla I, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, Marten J, Karaman I, Segura Lepe MP, O'Reilly PF, Knight J, Snieder H, Kato N, He J, Shyong Tai E, Abdullah Said M, Porteous D, Alver M, Poulter N, Farrall M, Gansevoort RT, Padmanabhan S, Magi R, Stanton A, Connell J, Bakker SJL, Metspalu A, Shields DC, Thom S, Brown M, Sever P, Esko T, Hayward C, van der Harst P, Saleheen D, Chowdhury R, Chambers JC, Chasman DI, Chakravarti A, Newton-Cheh C, Lindgren CM, Levy D, Kooner JS, Keavney B, Tomaszewski M, Samani NJ, Howson JMM, Tobin MD, Munroe PB, Ehret GB, Wain LV, Barnes MR, Tzoulaki I, Caulfield MJ, Elliott P, Wain V, Vaez A, Jansen R, Joehanes R, van der Most PJ, Mesut Erzurumluoglu A, O'Reilly P, 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, Fabiola Del Greco M, Ayers KL, Marrugat J, Ruggiero D, Lopez LM, Niiranen T, Enroth S, Jackson AU, Nelson CP, Huffman JE, Zhang W, Gandin I, Harris SE, Zemonik T, Lu Y, Shah N, de Borst MH, Mangino M, Prins BP, Campbell A, Li-Gao R, Chauhan G, Oldmeadow C, Abecasis G, Abedi M, Barbieri CM, Batini C, Blake T, Boehnke M, Bottinger EP, Braund PS, Brumat M, Campbell H, Cocca M, Collins F, Cordell HJ, Damman JJ, Davies G, de Geus EJ, de Mutsert R, Deelen J, Demirkale Y, Doney ASF, Dorr M, Ferreira T, Franberg M, Giedraitis V, Gieger C, Giulianini F, Gow AJ, Hamsten A, Harris TB, Hofman A, Holliday EG, 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, Milaneschi Y, Morgan A, Morris AD, Morrison AC, Munson PJ, Nandakumar P, Nguyen QT, Nutile T, Oldehinkel AJ, Oostra BA, Org E, Palotie A, Pare G, Pattie A, Penninx BWJH, Pramstaller PP, Raitakari OT, 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, Siscovick D, Sorice R, Stott DJ, Sundstrom J, Swertz M, Taylor KD, Tzourio C, Uitterlinden AG, Volker U, Vollenweider P, Wild S, Willemsen G, Wright AF, Yao J, Theriault S, Conen D, John A, Debette S, Mook-Kanamori DO, Zeggini E, Spector TD, Palmer CNA, Vergnaud A-C, Loos RJF, Polasek O, Starr JM, Girotto G, Lindgren CM, Vitart V, Tuomilehto J, Gyllensten U, Knekt P, Deary IJ, Ciullo M, Elosua R, Keavney BD, Hicks AA, Scott RA, Gasparini P, Laan M, Liu YM, 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, Wouter Jukema J, Strachan DP, Palmas W, Ingelsson E, Boomsma DI, Franco OH, Bochud M, Morris AP

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2017

Volume: 49

Issue: 3

Pages: 403-415

Online publication date: 30/01/2017

Acceptance date: 14/12/2016

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/ng.3768

DOI: 10.1038/ng.3768


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