Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/137674
Title: Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
Authors: Feitosa, Mary F.
Kraja, Aldi T.
Chasman, Daniel I.
Sung, Yun J.
Winkler, Thomas W.
Ntalla, Ioanna
Guo, Xiuqing
Franceschini, Nora
Cheng, Ching-Yu
Sim, Xueling
Vojinovic, Dina
Marten, Jonathan
Musani, Solomon K.
Li, Changwei
Bentley, Amy R.
Brown, Michael R.
Schwander, Karen
Richard, Melissa A.
Noordam, Raymond
Aschard, Hugues
Bartz, Traci M.
Bielak, Lawrence F.
Dorajoo, Rajkumar
Fisher, Virginia
Hartwig, Fernando P.
Horimoto, Andrea R. V. R.
Lohman, Kurt K.
Manning, Alisa K.
Rankinen, Tuomo
Smith, Albert V.
Tajuddin, Salman M.
Wojczynski, Mary K.
Alver, Maris
Boissel, Mathilde
Cai, Qiuyin
Campbell, Archie
Chai, Jin Fang
Chen, Xu
Divers, Jasmin
Gao, Chuan
Goel, Anuj
Hagemeijer, Yanick
Harris, Sarah E.
He, Meian
Hsu, Fang-Chi
Jackson, Anne U.
Kähönen, Mika
Kasturiratne, Anuradhani
Komulainen, Pirjo
Kühnel, Brigitte
Laguzzi, Federica
Luan, Jian'an
Matoba, Nana
Nolte, Ilja M.
Padmanabhan, Sandosh
Muhammad Riaz
Rueedi, Rico
Robino, Antonietta
Said, M. Abdullah
Scott, Robert A.
Sofer, Tamar
Stančáková, Alena
Takeuchi, Fumihiko
Tayo, Bamidele O.
van der Most, Peter J.
Varga, Tibor V.
Vitart, Veronique
Wang, Yajuan
Ware, Erin B.
Warren, Helen R.
Weiss, Stefan
Wen, Wanqing
Yanek, Lisa R.
Zhang, Weihua
Zhao, Jing Hua
Afaq, Saima
Amin, Najaf
Amini, Marzyeh
Arking, Dan E.
Aung, Tin
Boerwinkle, Eric
Borecki, Ingrid
Broeckel, Ulrich
Brown, Morris
Brumat, Marco
Burke, Gregory L.
Canouil, Mickaël
Chakravarti, Aravinda
Charumathi, Sabanayagam
Ida Chen, Yii-Der
Connell, John M.
Correa, Adolfo
de Las Fuentes, Lisa
de Mutsert, Renée
de Silva, H Janaka
Deng, Xuan
Ding, Jingzhong
Duan, Qing
Eaton, Charles B.
Ehret, Georg
Eppinga, Ruben N.
Evangelou, Evangelos
Faul, Jessica D.
Felix, Stephan B.
Forouhi, Nita G.
Forrester, Terrence
Franco, Oscar H.
Friedlander, Yechiel
Gandin, Ilaria
Gao, He
Ghanbari, Mohsen
Gigante, Bruna
Gu, C. Charles
Gu, Dongfeng
Hagenaars, Saskia P.
Hallmans, Göran
Harris, Tamara B.
He, Jiang
Heikkinen, Sami
Heng, Chew-Kiat
Hirata, Makoto
Howard, Barbara V
Ikram, M. Arfan
John, Ulrich
Katsuya, Tomohiro
Khor, Chiea Chuen
Kilpeläinen, Tuomas O.
Koh, Woon-Puay
Krieger, José E.
Kritchevsky, Stephen B.
Kubo, Michiaki
Kuusisto, Johanna
Lakka, Timo A.
Langefeld, Carl D.
Langenberg, Claudia
Launer, Lenore J.
Lehne, Benjamin
Lewis, Cora E.
Li, Yize
Lin, Shiow
Liu, Jianjun
Liu, Jingmin
Loh, Marie
Louie, Tin
Mägi, Reedik
McKenzie, Colin A.
Meitinger, Thomas
Metspalu, Andres
Milaneschi, Yuri
Milani, Lili
Mohlke, Karen L.
Momozawa, Yukihide
Nalls, Mike A.
Nelson, Christopher P.
Sotoodehnia, Nona
Norris, Jill M.
O'Connell, Jeff R.
Palmer, Nicholette D.
Perls, Thomas
Pedersen, Nancy L.
Peters, Annette
Peyser, Patricia A.
Poulter, Neil
Raffel, Leslie J.
Raitakari, Olli T.
Roll, Kathryn
Rose, Lynda M.
Rosendaal, Frits R.
Rotter, Jerome I.
Schmidt, Carsten O.
Schreiner, Pamela J.
Schupf, Nicole
Scott, William R.
Sever, Peter S.
Shi, Yuan
Sidney, Stephen
Sims, Mario
Sitlani, Colleen M.
Smith, Jennifer A.
Snieder, Harold
Starr, John M.
Strauch, Konstantin
Stringham, Heather M.
Tan, Nicholas Y. Q.
Tang, Hua
Taylor, Kent D.
Teo, Yik Ying
Tham, Yih Chung
Turner, Stephen T.
Uitterlinden, André G.
Vollenweider, Peter
Waldenberger, Melanie
Wang, Lihua
Wang, Ya Xing
Wei, Wen Bin
Williams, Christine
Yao, Jie
Yu, Caizheng
Yuan, Jian-Min
Zhao, Wei
Zonderman, Alan B.
Becker, Diane M.
Boehnke, Michael
Bowden, Donald W.
Chambers, John C.
Deary, Ian J.
Esko, Tõnu
Farrall, Martin
Franks, Paul W.
Freedman, Barry I.
Froguel, Philippe
Gasparini, Paolo
Gieger, Christian
Jonas, Jost Bruno
Kamatani, Yoichiro
Kato, Norihiro
Kooner, Jaspal S
Kutalik, Zoltán
Laakso, Markku
Laurie, Cathy C.
Leander, Karin
Lehtimäki, Terho
Study, Lifelines Cohort
Magnusson, Patrik K. E.
Oldehinkel, Albertine J.
Penninx, Brenda W. J. H.
Polasek, Ozren
Porteous, David J.
Rauramaa, 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
Bouchard, Claude
Christensen, Kaare
Evans, Michele K.
Gudnason, Vilmundur
Horta, Bernardo L.
Kardia, Sharon L. R.
Liu, Yongmei
Pereira, Alexandre C.
Psaty, Bruce M.
Ridker, Paul M.
van Dam, Rob M.
Gauderman, W. James
Zhu, Xiaofeng
Mook-Kanamori, Dennis O.
Fornage, Myriam
Rotimi, Charles N.
Cupples, L. Adrienne
Kelly, Tanika N.
Fox, Ervin R.
Hayward, Caroline
van Duijn, Cornelia M.
Tai, E. Shyong
Wong, Tien Yin
Kooperberg, Charles
Palmas, Walter
Rice, Kenneth
Morrison, Alanna C.
Elliott, Paul
Caulfield, Mark J.
Munroe, Patricia B.
Rao, Dabeeru C.
Province, Michael A.
Levy, Daniel
Keywords: Science::Medicine
Issue Date: 2018
Source: Feitosa, M. F., Kraja, A. T., Chasman, D. I., Sung, Y. J., Winkler, T. W., Ntalla, I., . . . Levy, D. (2018). Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. PloS one, 13(6), e0198166-. doi:10.1371/journal.pone.0198166
Journal: PloS one
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
URI: https://hdl.handle.net/10356/137674
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0198166
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © 2018 The Author(s) (Public Library of Science). This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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