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

Mary Feitosa (1) , Aldi Kraja (1) , Daniel Chasman (2, 3) , Yun Sung (1) , Thomas Winkler (4) , Ioanna Ntalla (5) , Xiuqing Guo (6) , Nora Franceschini (7) , Ching-Yu Cheng (8) , Xueling Sim (9) , Dina Vojinovic , Jonathan Marten , Solomon Musani , Changwei Li , Amy Bentley , Michael Brown , Karen Schwander , Melissa Richard , Raymond Noordam , Hugues Aschard (10, 11) , Traci Bartz , Lawrence Bielak , Rajkumar Dorajoo , Virginia Fisher , Fernando Hartwig , Andrea Horimoto , Kurt Lohman , Alisa Manning , Tuomo Rankinen , Albert Smith , Salman Tajuddin , Mary Wojczynski , Maris Alver , Mathilde Boissel (12, 13) , Qiuyin Cai , Archie Campbell , Jin Fang Chai , Xu Chen , Jasmin Divers , Chuan Gao , Anuj Goel , Yanick Hagemeijer , Sarah Harris , Meian He , Fang-Chi Hsu , Anne Jackson , Mika Kähönen , Anuradhani Kasturiratne , Pirjo Komulainen , Brigitte Kühnel , Federica Laguzzi , Jian'An Luan , Nana Matoba , Ilja Nolte , Sandosh Padmanabhan , Muhammad Riaz , Rico Rueedi , Antonietta Robino , M Abdullah Said , Robert Scott , Tamar Sofer , Alena Stančáková , Fumihiko Takeuchi , Bamidele Tayo , Peter van Der Most , Tibor Varga , Veronique Vitart , Yajuan Wang , Erin Ware , Helen Warren , Stefan Weiss , Wanqing Wen , Lisa Yanek , Weihua Zhang , Jing Hua Zhao , Saima Afaq , Najaf Amin , Marzyeh Amini , Dan Arking , Tin Aung , Eric Boerwinkle , Ingrid Borecki , Ulrich Broeckel , Morris Brown , Marco Brumat , Gregory Burke , Mickaël Canouil (12, 13) , Aravinda Chakravarti , Sabanayagam Charumathi , Yii-Der Ida Chen , John Connell , Adolfo Correa , Lisa de Las Fuentes , Renée de Mutsert , H Janaka de Silva , Xuan Deng , Jingzhong Ding , Qing Duan , Charles Eaton , Georg Ehret , Ruben Eppinga , Evangelos Evangelou , Jessica Faul , Stephan Felix , Nita Forouhi , Terrence Forrester , Oscar Franco , Yechiel Friedlander , Ilaria Gandin , He Gao , Mohsen Ghanbari , Bruna Gigante , C Charles Gu , Dongfeng Gu , Saskia Hagenaars , Göran Hallmans , Tamara Harris , Jiang He , Sami Heikkinen , Chew-Kiat Heng , Makoto Hirata , Barbara Howard , M Arfan Ikram , Ulrich John , Tomohiro Katsuya , Chiea Chuen Khor , Tuomas Kilpeläinen , Woon-Puay Koh , José Krieger , Stephen Kritchevsky , Michiaki Kubo , Johanna Kuusisto , Timo Lakka , Carl Langefeld , Claudia Langenberg , Lenore Launer , Benjamin Lehne , Cora Lewis , Yize Li , Shiow Lin , Jianjun Liu , Jingmin Liu , Marie Loh , Tin Louie , Reedik Mägi , Colin Mckenzie , Thomas Meitinger , Andres Metspalu , Yuri Milaneschi , Lili Milani , Karen Mohlke , Yukihide Momozawa , Mike Nalls , Christopher Nelson , Nona Sotoodehnia , Jill Norris , Jeff O'Connell , Nicholette Palmer , Thomas Perls , Nancy Pedersen , Annette Peters , Patricia Peyser , Neil Poulter , Leslie Raffel , Olli Raitakari , Kathryn Roll , Lynda Rose , Frits Rosendaal , Jerome Rotter , Carsten Schmidt , Pamela Schreiner , Nicole Schupf , William Scott , Peter Sever , Yuan Shi , Stephen Sidney , Mario Sims , Colleen Sitlani , Jennifer Smith , Harold Snieder , John Starr , Konstantin Strauch , Heather Stringham , Nicholas Tan , Hua Tang , Kent Taylor , Yik Ying Teo , Yih Chung Tham , Stephen Turner , André 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 Zonderman , Diane Becker , Michael Boehnke , Donald Bowden , John Chambers , Ian Deary , Tõnu Esko , Martin Farrall , Paul Franks , Barry Freedman , Philippe Froguel (13, 12) , Paolo Gasparini , Christian Gieger , Jost Bruno Jonas , Yoichiro Kamatani , Norihiro Kato , Jaspal Kooner , Zoltán Kutalik , Markku Laakso , Cathy Laurie , Karin Leander , Terho Lehtimäki , Lifelines Cohort Study , Patrik Magnusson , Albertine Oldehinkel , Brenda Penninx , Ozren Polasek , David Porteous , Rainer Rauramaa , Nilesh Samani , James Scott , Xiao-Ou Shu , Pim van Der Harst , Lynne Wagenknecht , Nicholas Wareham , Hugh Watkins , David Weir , Ananda Wickremasinghe , Tangchun Wu , Wei Zheng , Claude Bouchard , Kaare Christensen , Michele Evans , Vilmundur Gudnason , Bernardo Horta , Sharon Kardia , Yongmei Liu , Alexandre Pereira , Bruce Psaty , Paul Ridker , Rob van Dam , W James Gauderman , Xiaofeng Zhu , Dennis Mook-Kanamori , Myriam Fornage , Charles Rotimi , L Adrienne Cupples , Tanika Kelly , Ervin Fox , Caroline Hayward , Cornelia van Duijn , E Shyong Tai , Tien Yin Wong , Charles Kooperberg , Walter Palmas , Kenneth Rice , Alanna Morrison , Paul Elliott , Mark Caulfield , Patricia Munroe , Dabeeru Rao , Michael Province , Daniel Levy (14)

1 Washington University School of Medicine in St. Louis
2 Brigham and Women's Hospital [Boston]
3 HMS - Harvard Medical School [Boston]
4 University of Regensburg
5 QMUL - Queen Mary University of London
6 Harbor UCLA Medical Center [Torrance, Ca.]
7 Department of Epidemiology
8 NPU - Northwestern Polytechnical University [Xi'an]
9 Centre for Molecular Epidemiology
10 Harvard School of Public Health
11 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
12 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
13 Institut Pasteur de Lille
14 NIH - National Institutes of Health [Bethesda]

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.

Domains: Human genetics; Santé publique et épidémiologie; Methodology [stat.ME]; Applications [stat.AP]; Bioinformatics [q-bio.QM]

Mary Feitosa, Aldi Kraja, Daniel Chasman, Yun Sung, Thomas Winkler, et al.. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. PLoS ONE, 2018, 13 (6), pp.e0198166. ⟨10.1371/journal.pone.0198166⟩. ⟨pasteur-03278584⟩