Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Mary F. Feitosa, Aldi T. Kraja, Daniel I. Chasman, Yun J. Sung, Thomas W. Winkler, Ioanna Ntalla, Xiuqing Guo, Nora Franceschini, Ching Yu Cheng, Xueling Sim, Dina Vojinovic, Jonathan Marten, Solomon K. Musani, Changwei Li, Amy R. Bentley, Michael R. Brown, Karen Schwander, Melissa A. Richard, Raymond Noordam, Hugues AschardTraci M. Bartz, Lawrence F. Bielak, Rajkumar Dorajoo, Virginia Fisher, Fernando P. Hartwig, Andrea R.V.R. Horimoto, Kurt K. Lohman, Alisa K. Manning, Tuomo Rankinen, Albert V. Smith, Salman M. Tajuddin, Mary K. Wojczynski, Maris Alver, Mathilde Boissel, Qiuyin Cai, Archie Campbell, Jin Fang Chai, Xu Chen, Jasmin Divers, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E. Harris, Meian He, Fang Chi Hsu, Anne U. Jackson, Mika Kähönen, Anuradhani Kasturiratne, Pirjo Komulainen, Brigitte Kühnel, Federica Laguzzi, Jian'An Luan, Nana Matoba, Ilja M. Nolte, Sandosh Padmanabhan, Muhammad Riaz, Rico Rueedi, Antonietta Robino, M. Abdullah Said, Robert A. Scott, Tamar Sofer, Alena Stančáková, Fumihiko Takeuchi, Bamidele O. Tayo, Peter J. Van Der Most, Tibor V. Varga, Veronique Vitart, Yajuan Wang, Erin B. Ware, Helen R. Warren, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Najaf Amin, Marzyeh Amini, Dan E. Arking, Tin Aung, Eric Boerwinkle, Ingrid Borecki, Ulrich Broeckel, Morris Brown, Marco Brumat, Gregory L. Burke, Mickaël Canouil, Aravinda Chakravarti, Sabanayagam Charumathi, Yii Der Ida Chen, John M. Connell, Adolfo Correa, Lisa De Las Fuentes, Renée De Mutsert, H. Janaka De Silva, Xuan Deng, Jingzhong Ding, Qing Duan, Charles B. Eaton, Georg Ehret, Ruben N. Eppinga, Evangelos Evangelou, Jessica D. Faul, Stephan B. Felix, Nita G. Forouhi, Terrence Forrester, Oscar H. Franco, Yechiel Friedlander, Ilaria Gandin, He Gao, Mohsen Ghanbari, Bruna Gigante, C. Charles Gu, Dongfeng Gu, Saskia P. Hagenaars, Göran Hallmans, Tamara B. Harris, Jiang He, Sami Heikkinen, Chew Kiat Heng, Makoto Hirata, Barbara V. Howard, M. Arfan Ikram, Ulrich John, Tomohiro Katsuya, Chiea Chuen Khor, Tuomas O. Kilpeläinen, Woon Puay Koh, José E. Krieger, Stephen B. Kritchevsky, Michiaki Kubo, Johanna Kuusisto, Timo A. Lakka, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Benjamin Lehne, Cora E. Lewis, Yize Li, Shiow Lin, Jianjun Liu, Jingmin Liu, Marie Loh, Tin Louie, Reedik Mägi, Colin A. McKenzie, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Lili Milani, Karen L. Mohlke, Yukihide Momozawa, Mike A. Nalls, Christopher P. Nelson, Nona Sotoodehnia, Jill M. Norris, Jeff R. O'Connell, Nicholette D. Palmer, Thomas Perls, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Neil Poulter, Leslie J. Raffel, Olli T. Raitakari, Kathryn Roll, Lynda M. Rose, Frits R. Rosendaal, Jerome I. Rotter, Carsten O. Schmidt, Pamela J. Schreiner, Nicole Schupf, William R. Scott, Peter S. Sever, Yuan Shi, Stephen Sidney, Mario Sims, Colleen M. Sitlani, Jennifer A. Smith, Harold Snieder, John M. Starr, Konstantin Strauch, Heather M. Stringham, Nicholas Y.Q. Tan, Hua Tang, Kent D. Taylor, Yik Ying Teo, Yih Chung Tham, Stephen T. Turner, André G. Uitterlinden, Peter Vollenweider, Melanie Waldenberger, Lihua Wang, Ya Xing Wang, Wen Bin Wei, Christine Williams, Jie Yao, Caizheng Yu, Jian Min Yuan, Wei Zhao, Alan B. Zonderman, Diane M. Becker, Michael Boehnke, Donald W. Bowden, John C. Chambers, Ian J. Deary, Tõnu Esko, Martin Farrall, Paul W. Franks, Barry I. Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Jost Bruno Jonas, Yoichiro Kamatani, Norihiro Kato, Jaspal S. Kooner, Zoltán Kutalik, Markku Laakso, Cathy C. Laurie, Karin Leander, Terho Lehtimäki, Patrik K.E. Magnusson, Albertine J. Oldehinkel, Brenda W.J.H. Penninx, Ozren Polasek, David J. Porteous, Rainer Rauramaa, Nilesh J. Samani, James Scott, Xiao Ou Shu, Pim Van Der Harst, Lynne E. Wagenknecht, Nicholas J. Wareham, Hugh Watkins, David R. Weir, Ananda R. Wickremasinghe, Tangchun Wu, Wei Zheng, Claude Bouchard, Kaare Christensen, Michele K. Evans, Vilmundur Gudnason, Bernardo L. Horta, Sharon L.R. Kardia, Yongmei Liu, Alexandre C. Pereira, Bruce M. Psaty, Paul M. Ridker, Rob M. Van Dam, W. James Gauderman, Xiaofeng Zhu, Dennis O. Mook-Kanamori, Myriam Fornage, Charles N. Rotimi, L. Adrienne Cupples, Tanika N. Kelly, Ervin R. Fox, Caroline Hayward, Cornelia M. Van Duijn, E. Shyong Tai, Tien Yin Wong, Charles Kooperberg, Walter Palmas, Kenneth Rice, Alanna C. Morrison, Paul Elliott, Mark J. Caulfield, Patricia B. Munroe, Dabeeru C. Rao, Michael A. Province, Daniel Levy

Research output: Contribution to journalArticle

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 × 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 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 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.

Original languageEnglish (US)
Article numbere0198166
JournalPloS one
Volume13
Issue number6
DOIs
StatePublished - Jun 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Feitosa, M. F., Kraja, A. T., Chasman, D. I., Sung, Y. J., Winkler, T. W., Ntalla, I., Guo, X., Franceschini, N., Cheng, C. Y., Sim, X., Vojinovic, D., Marten, J., Musani, S. K., Li, C., Bentley, A. R., Brown, M. R., Schwander, K., Richard, M. A., Noordam, R., ... 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]. https://doi.org/10.1371/journal.pone.0198166