A Large-Scale Multi-Ancestry Genome-Wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

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Sung, Yun J.; Winkler, Thomas W.; de Las Fuentes, Lisa; Bentley, Amy R.; Brown, Michael R.; Kraja, Aldi T.; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; & Franceschini, Nora, et al. (2018). A Large-Scale Multi-Ancestry Genome-Wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. American Journal of Human Genetics, 102(3), 375-400. PMCID: PMC5985266

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 < 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 < 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).

URL

http://dx.doi.org/10.1016/j.ajhg.2018.01.015

Reference Type

Journal Article

Year Published

2018

Journal Title

American Journal of Human Genetics

Author(s)

Sung, Yun J.
Winkler, Thomas W.
de Las Fuentes, Lisa
Bentley, Amy R.
Brown, Michael R.
Kraja, Aldi T.
Schwander, Karen
Ntalla, Ioanna
Guo, Xiuqing
Franceschini, Nora
Lu, Yingchang
Cheng, Ching-Yu
Sim, Xueling
Vojinovic, Dina
Marten, Jonathan
Musani, Solomon K.
Li, Changwei
Feitosa, Mary F.
Kilpelainen, Tuomas O.
Richard, Melissa A.
Noordam, Raymond
Aslibekyan, Stella
Aschard, Hugues
Bartz, Traci M.
Dorajoo, Rajkumar
Liu, Yongmei
Manning, Alisa K.
Rankinen, Tuomo
Smith, Albert V.
Tajuddin, Salman M.
Tayo, Bamidele O.
Warren, Helen R.
Zhao, Wei
Zhou, Yanhua
Matoba, Nana
Sofer, Tamar
Alver, Maris
Amini, Marzyeh
Boissel, Mathilde
Chai, Jin Fang
Chen, Xu
Divers, Jasmin
Gandin, Ilaria
Gao, Chuan
Giulianini, Franco
Goel, Anuj
Harris, Sarah E.
Hartwig, Fernando Pires
Horimoto, Andrea R. V. R.
Hsu, Fang-Chi
Jackson, Anne U.
Kahonen, Mika
Kasturiratne, Anuradhani
Kuhnel, Brigitte
Leander, Karin
Lee, Wen-Jane
Lin, Keng-Hung
Luan, Jian'an
McKenzie, Colin A.
Meian, He
Nelson, Christopher P.
Rauramaa, Rainer
Schupf, Nicole
Scott, Robert A.
Sheu, Wayne Huey-Herng
Stancakova, Alena
Takeuchi, Fumihiko
van der Most, Peter J.
Varga, Tibor V.
Wang, Heming
Wang, Yajuan
Ware, Erin B.
Weiss, Stefan
Wen, Wanqing
Yanek, Lisa R.
Zhang, Weihua
Zhao, Jing Hua
Afaq, Saima
Alfred, Tamuno
Amin, Najaf
Arking, Dan E.
Aung, Tin
Barr, R. Graham
Bielak, Lawrence F.
Boerwinkle, Eric A.
Bottinger, Erwin P.
Braund, Peter S.
Brody, Jennifer A.
Broeckel, Ulrich
Cabrera, Claudia P.
Cade, Brian E.
Caizheng, Yu
Campbell, Archie
Canouil, Mickael
Chakravarti, Aravinda
CHARGE Neurology Working Group,
Chauhan, Ganesh
Christensen, Kaare
Cocca, Massimiliano
COGENT-Kidney Consortium,
Collins, Francis S.
Connell, John M.
de Mutsert, Renee
de Silva, H. Janaka
Debette, Stephanie
Dorr, Marcus
Duan, Qing
Eaton, Charles B.
Ehret, Georg B.
Evangelou, Evangelos
Faul, Jessica D.
Fisher, Virginia A.
Forouhi, Nita G.
Franco, Oscar H.
Friedlander, Yechiel
Gao, He
GIANT Consortium,
Gigante, Bruna
Graff, Mariaelisa
Gu, C. Charles
Gu, Dongfeng
Gupta, Preeti
Hagenaars, Saskia P.
Harris, Tamara B.
He, Jiang
Heikkinen, Sami
Heng, Chew-Kiat
Hirata, Makoto
Hofman, Albert
Howard, Barbara V.
Hunt, Steven C.
Irvin, Marguerite Ryan
Jia, Yucheng
Joehanes, Roby
Justice, Anne E.
Katsuya, Tomohiro
Kaufman, Joel D.
Kerrison, Nicola D.
Khor, Chiea Chuen
Koh, Woon-Puay
Koistinen, Heikki A.
Komulainen, Pirjo
Kooperberg, Charles L.
Krieger, Jose E.
Kubo, Michiaki
Kuusisto, Johanna
Langefeld, Carl D.
Langenberg, Claudia
Launer, Lenore J.
Lehne, Benjamin
Lewis, Cora E.
Li, Yize
Lifelines Cohort Study,
Lim, Sing Hui
Lin, Shiow
Liu, Ching-Ti
Liu, Jianjun
Liu, Jingmin
Liu, Kiang
Liu, Yeheng
Loh, Marie
Lohman, Kurt K.
Long, Jirong
Louie, Tin
Magi, Reedik
Mahajan, Anubha
Meitinger, Thomas
Metspalu, Andres
Milani, Lili
Momozawa, Yukihide
Morris, Andrew P.
Mosley, Thomas H., Jr.
Munson, Peter
Murray, Alison D.
Nalls, Mike A.
Nasri, Ubaydah
Norris, Jill M.
North, Kari E.
Ogunniyi, Adesola
Padmanabhan, Sandosh
Palmas, Walter
Palmer, Nicholette D.
Pankow, James S.
Pedersen, Nancy L.
Peters, Annette
Peyser, Patricia A.
Polasek, Ozren
Raitakari, Olli T.
Renstrom, Frida
Rice, Treva K.
Ridker, Paul M.
Robino, Antonietta
Robinson, Jennifer G.
Rose, Lynda M.
Rudan, Igor
Sabanayagam, Charumathi
Salako, Babatunde
Sandow, Kevin
Schmidt, Carsten O.
Schreiner, Pamela J.
Scott, William R.
Seshadri, Sudha
Sever, Peter
Sitlani, Colleen M.
Smith, Jennifer A.
Snieder, Harold
Starr, John M.
Strauch, Konstantin
Tang, Hua
Taylor, Kent D.
Teo, Yik Ying
Tham, Yih Chung
Uitterlinden, Andre G.
Waldenberger, Melanie
Wang, Lihua
Wang, Ya Xing
Wei, Wen Bin
Williams, Christine
Wilson, Gregory, Sr.
Wojczynski, Mary K.
Yao, Jie
Yuan, Jian-Min
Zonderman, Alan B.
Becker, Diane M.
Boehnke, Michael
Bowden, Donald W.
Chambers, John C.
Chen, Yii-Der Ida
de Faire, Ulf
Deary, Ian J.
Esko, Tonu
Farrall, Martin
Forrester, Terrence
Franks, Paul W.
Freedman, Barry I.
Froguel, Philippe
Gasparini, Paolo
Gieger, Christian
Horta, Bernardo L.
Hung, Yi-Jen
Jonas, Jost B.
Kato, Norihiro
Kooner, Jaspal Singh S.
Laakso, Markku
Lehtimaki, Terho
Liang, Kae-Woei
Magnusson, Patrik K. E.
Newman, Anne B.
Oldehinkel, Albertine J.
Pereira, Alexandre C.
Redline, Susan S.
Rettig, Rainer
Samani, Nilesh J.
Scott, James
Shu, Xiao-Ou
van der Harst, Pim
Wagenknecht, Lynne E.
Wareham, Nicholas J.
Watkins, Hugh
Weir, David R.
Wickremasinghe, Ananda R.
Wu, Tangchun
Zheng, Wei
Kamatani, Yoichiro
Laurie, Cathy C.
Bouchard, Claude
Cooper, Richard S.
Evans, Michele K.
Gudnason, Vilmundur G.
Kardia, Sharon L. R.
Kritchevsky, Stephen B.
Levy, Daniel
O'Connell, Jeffrey R.
Psaty, Bruce M.
van Dam, Rob M.
Sims, Mario
Arnett, Donna K.
Mook-Kanamori, Dennis O.
Kelly, Tanika N.
Fox, Ervin R.
Hayward, Caroline
Fornage, Myriam
Rotimi, Charles N.
Province, Michael A.
van Duijn, Cornelia M.
Tai, E. Shyong
Wong, Tien Yin
Loos, Ruth J. F.
Reiner, Alexander P.
Rotter, Jerome I.
Zhu, Xiaofeng
Bierut, Laura J.
Gauderman, W. James
Caulfield, Mark J.
Elliott, Paul
Rice, Kenneth M.
Munroe, Patricia B.
Morrison, Alanna C.
Cupples, L. Adrienne
Rao, Dabeeru C.
Chasman, Daniel I.

PMCID

PMC5985266

ORCiD

Graff - 0000-0001-6380-1735