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A large-scale multi-ancestry genome-wide study accounting for smoking behavior identifies multiple significant loci for blood pressure

Show simple item record Sung, Y.J. en_US Winkler, T.W. en_US de Las Fuentes, L. en_US Bentley, A.R. en_US Brown, M.R. en_US Kraja, A.T. en_US Schwander, K. en_US Ntalla, I. en_US Guo, X. en_US Franceschini, N. en_US Lu, Y. en_US Cheng, C.Y. en_US Sim, X. en_US Vojinovic, D. en_US Marten, J. en_US Musani, S.K. en_US Li, C. en_US Feitosa, M.F. en_US Kilpelainen, T.O. en_US Richard, M.A. en_US Noordam, R. en_US Aslibekyan, S. en_US Aschard, H. en_US Bartz, T.M. en_US Dorajoo, R. en_US Liu, Y. en_US Manning, A.K. en_US Rankinen, T. en_US Smith, A.V. en_US Tajuddin, S.M. en_US Tayo, B.O. en_US Warren, H.R. en_US Zhao, W. en_US Zhou, Y. en_US Matoba, N. en_US Sofer, T. en_US Alver, M. en Amini, M. en_US Boissel, M. en_US Chai, J.F. en_US Chen, X. en_US Divers, J. en_US Gandin, I. en_US Gao, C. en_US Giulianini, F. en_US Goel, A. Harris, S.E. en_US Hatwig, F.P. en_US Horimoto, A.R.V.R. en_US Hsu, F.C. en_US Jackson, A.U. en_US Kahonen, M. Kasturiratne, A. Kuhnel, B. Leander, K. Lee, W.J. Lin, K.H. an Luan, J. McKenzie, C.A. Meian, H. Nelson, C.P. Rauramaa, R. Schupf, N. Scott, R.A. Sheu, W.H.H. Stancakova, A. Takeuchi, F. van der Most, P.J. Varga, T.V. Wang, H. Wang, Y. Ware, E.B. Weiss, S. Wen, W. Yanek, L.R. Zhang, W. Zhao, J.H. Afag, S. Alfred, T. Amin, N. Arking, D. Aung, T. Barr, R.G. Bielak, L.F. Boerwincle, E. Bottinger, E.P. Braund, P.S. Brody, J.A. Broeckel, U. Cabrera, C.P. Cade, B. Caizheng, Y. Campbell, A. Canouil, M. Chakravarti, A. CHARGE Neurology Working Group Chauhan, G. Christensen, K. Cocca, M. COGENT-Kidney Consortium Collins, F.S. Connel, J.M. de Mutsert, R. de Silva, H.J. Debette, S. Dorr, M. Duan, Q. Eaton, C.B. Ehret, G. Evangelou, E. FAul, J.D. Fisher, V.A. Forouhi, N.G. Franco, O.H. Friedlander, Y. Gao, H. GIANT Consortium Gigante, B. Graff, M. Gu, C.C. Gu, D. Gupta, P. Hagenaars, S.P. Harris, T.B. He, J. Heikkinen, S. Heng, C.K. Hirata, M. Hofman., A. Howard, B.V. Hunt, S. Irvin, M.R. Jia, Y. Joehanes, R. Justice, A.E. Katsuya, T. Kaufman, J, Kerrison, N.D. Khor, C.C. Koh, W.P. Koistinen, H.A. Komulainen, P. Kooperberg, C. Krieger, J.E. Kubo, M. Kuusisto, J. Lanefeld, C.D. Langenberg, C. Launer, L.J. Lehne, B. Lewis, C.E. Li, Y. Lifelines Cohort Study Lim, S.H. Lin, S. Liu, C.T. Liu, J. Liu, J. Liu, K. Liu, Y. Loh, M. Lohmann, K.K. Long, J. Louie, T. Magi, R. Mahajan, A. Meitinger, T. Metspalu, A. Milani, L. Momozawa, Y. Morris, A.P. Mosley, T.H.Jr. Munson, P. Murray, A.D. Nalls, M.A. Nasri, U. Norris, J.M. North, K. Ogunniyi, A. Padmanabhan, S. Palmas, W.R. Palmer, N.D. Pankow, J.S. Pedersen, N.L. Peters, A. Peyser, P.A. Polasek, O. Raitakari, O.T. Renstrom, F. Rice, T.K. Ridker, P.M. Robino, A. Robinson, J.G. Rose, L.M. Rudan, I. Salako, B.L. Sandow, K. Schmidt, C.O. Schreiner, P.J. Scott, W.R. Seshadri, S. Sever, P. Sitlani, C.M. Smith, J.A. Snieder, H. Starr, J.M. Strauch, K. Tang, H. Taylor, K.D. Teo, Y.Y. Tham, Y.C. Uitterlineden, A.G. Waldenberger, M. Wang, L. Wang, Y.X. Wei, W.B. Williams, C. Wilson, G. Wojczynski, M.K. Yao, J. Yuan, J.M. Zonderman, A.B. Becker, D.M. Boehnke, M. Bowden, D.W. Chambers, J.C. Chen, Y.I. de Faire, U. Deary, I.J. Esco, T. Farrall, M. Forrester, T. Franks, P.W. Freedman, B.I. Froguel, P. Gasparini, P. Gieger, C. Horta, B.L. Hung, Y.J. Jonas, J.B. Kato, N. Kooner, J.S. Laakso, M. Lehtimaki, T. Liang, K.W. Magnusson, P.K.E. Newman, A.B. Oldehinkel, A.J. Pereira, A.C. Redline, S. Rettig, R. Samani, N.J. Scott, J. Shu, X.O. van der Harst, P. Wagenknecht, L.E. Wareham, N.J. Watkins, H. Weir, D.R. Wickremasinghe, A.R. Wu, T. Zheng, W. Kamatani, Y. Laurie, C.C. Bouchard, C. Cooper, R.S. Evans, M.K. Gudnason, V. Kardia, S.L.R. Kritchevsky, S.B. Levy, D. O'Connell, J.R. Psaty, B.M. van Dam, R.M. Sims, M. Arnett, D.K. Mook-Kanamori, D.O. Kelly, T.N. Fox, E.R. Hayward, C. Fornage, M. Rotimi, C.N. Province, M.A. van Dujin, C.M. Tai, E.S. Wong, T.Y. Loos, R.J.F. Reiner, A.P. Rotter, J.I. Zhu, X. Bierut, L.J. Gauderman, W.J. Caulfield, M.J. Elliott, P. Rice, K. Munroe, P.B. Morrison, A.C. Cupples, L.A. Rao., D.C. Chasman, D.I. 2018-03-09T05:38:22Z 2018-03-09T05:38:22Z 2018
dc.identifier.citation American journal of human genetics.2018;102(3):375-400 en_US
dc.identifier.issn 0002-9297 (Print)
dc.identifier.issn 1537-6605 (Electronic)
dc.identifier.issn 0002-9297 (Linking)
dc.description Indexed In MEDLINE en_US
dc.description.abstract Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2). en_US
dc.language.iso en_US en_US
dc.publisher University of Chicago Press en_US
dc.subject Blood pressure en_US
dc.title A large-scale multi-ancestry genome-wide study accounting for smoking behavior identifies multiple significant loci for blood pressure en_US
dc.type Article en_US

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