A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure Journal Article

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Authors: Sung, Y. J.; Winkler, T. W.; de Las Fuentes, L; Bentley, A. R.; Brown, M. R.; Kraja, A. T.; Schwander, K; Ntalla, I; Guo, X; Franceschini, N; Lu, Y; Cheng, C. Y.; Sim, X; Vojinovic, D; Marten, J; Musani, S. K.; Li, C; Feitosa, M. F.; Kilpelainen, T. O.; Richard, M. A.; Noordam, R; Aslibekyan, S; Aschard, H; Bartz, T. M.; Dorajoo, R; Liu, Y; Manning, A. K.; Rankinen, T; Smith, A. V.; Tajuddin, S. M.; Tayo, B. O.; Warren, H. R.; Zhao, W; Zhou, Y; Matoba, N; Sofer, T; Alver, M; Amini, M; Boissel, M; Chai, J. F.; Chen, X; Divers, J; Gandin, I; Gao, C; Giulianini, F; Goel, A; Harris, S. E.; Hartwig, F. P.; Horimoto, A. R. V. R.; Hsu, F. C.; Jackson, A. U.; 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.; Afaq, S; Alfred, T; Amin, N; Arking, D.; Aung, T; Barr, R. G.; Bielak, L. F.; Boerwinkle, 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.; Connell, 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; Langefeld, 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, K; Loh, M; Lohman, K. K.; Long, J; Louie, T; Magi, R.; Mahajan, A; Meitinger, T; Metspalu, A; Milani, L; Momozawa, Y; Morris, A. P.; Mosley TH, 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; Sabanayagam, C; 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.; Uitterlinden, 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.; Esko, 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 Duijn, 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.
Article Title: A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure
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 approximately 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 lt; 5 x 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 lt; 5 x 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).
Journal Title: American Journal of Human Genetics
Volume: 102
Issue: 3
ISSN: 1537-6605; 0002-9297
Publisher: American Society of Human Genetics  
Journal Place: United States
Date Published: 2018
Start Page: 375
End Page: 400
Language: eng
DOI/URL:

S0002-9297(18)30017-X
Notes: LR: 20180329; CI: Copyright (c) 2018; GR: R01 HL105756/HL/NHLBI NIH HHS/United States; GR: R01 MD012765/MD/NIMHD NIH HHS/United States; GR: R21 HL123677/HL/NHLBI NIH HHS/United States; GR: U01 AG009740/AG/NIA NIH HHS/United States; JID: 0370475; OTO: NOTNLM; 2017/10/10 00:00 [received]; 2018/01/18 00:00 [accepted]; 2018/02/20 06:00 [pubmed]; 2018/02/20 06:00 [medline]; 2018/02/20 06:00 [entrez]; ppublish