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

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  • Feitosa, M.F.
    • Other Affiliation: Washington University School of Medicine
  • Kraja, A.T.
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  • Chasman, D.I.
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  • Franceschini, N.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Cheng, C.-Y.
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  • Bentley, A.R.
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    • Other Affiliation: Genome Institute of Singapore
  • Fisher, V.
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  • Lohman, K.K.
    • Other Affiliation: Wake Forest School of Medicine
  • Manning, A.K.
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  • Rankinen, T.
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  • Alver, M.
    • Other Affiliation: University of Tartu
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    • Other Affiliation: Vanderbilt University School of Medicine
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    • Other Affiliation: National University of Singapore
  • Chen, X.
    • Other Affiliation: Karolinska Institutet
  • Divers, J.
    • Other Affiliation: Wake Forest School of Medicine
  • Gao, C.
    • Other Affiliation: Wake Forest School of Medicine
  • Goel, A.
    • Other Affiliation: University of Oxford
  • Hagemeijer, Y.
    • Other Affiliation: University of Groningen
  • Harris, S.E.
    • Other Affiliation: University of Edinburgh
  • He, M.
    • Other Affiliation: Huazhong University of Science and Technology
  • Hsu, F.-C.
    • Other Affiliation: Wake Forest School of Medicine
  • Jackson, A.U.
    • Other Affiliation: University of Michigan
  • Kähönen, M.
    • Other Affiliation: University of Tampere
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    • Other Affiliation: University of Kelaniya
  • Komulainen, P.
    • Other Affiliation: Kuopio Research Institute of Exercise Medicine
  • Kühnel, B.
    • Other Affiliation: Helmholtz Zentrum München
  • Laguzzi, F.
    • Other Affiliation: Karolinska Institutet
  • Luan, J.
    • Other Affiliation: University of Cambridge
  • Matoba, N.
    • Other Affiliation: RIKEN
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    • Other Affiliation: University of Groningen
  • Padmanabhan, S.
    • Other Affiliation: University of Glasgow
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    • Other Affiliation: University of Leicester
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    • Other Affiliation: University of Groningen
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    • Other Affiliation: University of Cambridge
  • Sofer, T.
    • Other Affiliation: Harvard Medical School
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    • Other Affiliation: University of Eastern Finland
  • Takeuchi, F.
    • Other Affiliation: National Center for Global Health and Medicine
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    • Other Affiliation: Loyola University Chicago
  • Van Der Most, P.J.
    • Other Affiliation: University of Groningen
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    • Other Affiliation: Skåne University Hospital
  • Vitart, V.
    • Other Affiliation: University of Edinburgh
  • Wang, Y.
    • Other Affiliation: Case Western Reserve University
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    • Other Affiliation: University of Michigan
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    • Other Affiliation: Queen Mary University of London
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    • Other Affiliation: University Greifsald
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    • Other Affiliation: Vanderbilt University School of Medicine
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    • Other Affiliation: Johns Hopkins University School of Medicine
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    • Other Affiliation: Imperial College London
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    • Other Affiliation: University of Cambridge
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    • Other Affiliation: Imperial College London
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    • Other Affiliation: Erasmus University Medical Center
  • Amini, M.
    • Other Affiliation: University of Groningen
  • Arking, D.E.
    • Other Affiliation: Johns Hopkins University
  • Aung, T.
    • Other Affiliation: Singapore Eye Research Institute
  • Boerwinkle, E.
    • Other Affiliation: University of Texas School of Public Health
  • Borecki, I.
    • Other Affiliation: Washington University
  • Broeckel, U.
    • Other Affiliation: Medical College of Wisconsin
  • Brown, M.
    • Other Affiliation: Queen Mary University of London
  • Brumat, M.
    • Other Affiliation: University of Trieste
  • Burke, G.L.
    • Other Affiliation: Wake Forest School of Medicine
  • Canouil, M.
    • Other Affiliation: University of Lille
  • Chakravarti, A.
    • Other Affiliation: Johns Hopkins University
  • Charumathi, S.
    • Other Affiliation: Singapore Eye Research Institute
  • Chen, Y.-D.I.
    • Other Affiliation: LABioMed at Harbor-UCLA Medical Center
  • Connell, J.M.
    • Other Affiliation: University of Dundee
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    • Other Affiliation: University of Mississippi Medical Center
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  • De Mutsert, R.
    • Other Affiliation: Leiden University Medical Center
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    • Other Affiliation: University of Kelaniya
  • Deng, X.
    • Other Affiliation: Boston University
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    • Other Affiliation: Wake Forest University Health Sciences
  • Duan, Q.
    • Affiliation: School of Medicine, Department of Genetics
  • Eaton, C.B.
    • Other Affiliation: Brown University
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    • Other Affiliation: Geneva University Hospital
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    • Other Affiliation: University of Groningen
  • Evangelou, E.
    • Other Affiliation: Imperial College London
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    • Other Affiliation: University of Michigan
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    • Other Affiliation: University Medicine Greifswald
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    • Other Affiliation: University of Cambridge
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    • Other Affiliation: University of the West Indies
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    • Other Affiliation: Erasmus University Medical Center
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    • Other Affiliation: Hebrew University-Hadassah Medical Center
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    • Other Affiliation: University of Trieste
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    • Other Affiliation: Imperial College London
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    • Other Affiliation: Mashhad University of Medical Sciences
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    • Other Affiliation: Karolinska Institutet
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    • Other Affiliation: Washington University School of Medicine
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    • Other Affiliation: Peking Union Medical College
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    • Other Affiliation: Umeå University
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    • Other Affiliation: National Institutes of Health
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    • Other Affiliation: Tulane University
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    • Other Affiliation: University of Eastern Finland
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    • Other Affiliation: University of Tokyo
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    • Other Affiliation: MedStar Health Research Institute
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    • Other Affiliation: Osaka University Graduate School of Medicine
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    • Other Affiliation: University of Copenhagen
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    • Other Affiliation: National University Health System and National University of Singapore
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    • Other Affiliation: University of Eastern Finland
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    • Other Affiliation: Wake Forest School of Medicine
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    • Other Affiliation: University of Alabama at Birmingham
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    • Other Affiliation: Imperial College London
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    • Other Affiliation: University of Washington
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    • Other Affiliation: Helmholtz Zentrum München
  • Metspalu, A.
    • Other Affiliation: University of Tartu
  • Milaneschi, Y.
    • Other Affiliation: VU University Medical Center
  • Milani, L.
    • Other Affiliation: University of Tartu
  • Mohlke, K.L.
    • Affiliation: School of Medicine, Department of Genetics
  • Momozawa, Y.
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  • Nalls, M.A.
    • Other Affiliation: National Institute on Aging
  • Nelson, C.P.
    • Other Affiliation: University of Leicester
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    • Other Affiliation: Karolinska Institutet
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    • Other Affiliation: University of Michigan
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    • Other Affiliation: Turku University Hospital
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  • Rose, L.M.
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  • Schmidt, C.O.
    • Other Affiliation: University Medicine Greifswald
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  • Sever, P.S.
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    • Other Affiliation: Singapore National Eye Centre
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    • Other Affiliation: Kaiser Permanente of Northern California
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  • Stringham, H.M.
    • Other Affiliation: University of Michigan
  • Tan, N.Y.Q.
    • Other Affiliation: Singapore National Eye Centre
  • Tang, H.
    • Other Affiliation: Stanford University
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    • Other Affiliation: LABioMed at Harbor-UCLA Medical Center
  • Teo, Y.Y.
    • Other Affiliation: National University of Singapore
  • Tham, Y.C.
    • Other Affiliation: Singapore National Eye Centre
  • Turner, S.T.
    • Other Affiliation: Mayo Clinic
  • Uitterlinden, A.G.
    • Other Affiliation: Erasmus University Medical Center
  • Vollenweider, P.
    • Other Affiliation: University Hospital, Lausanne
  • Waldenberger, M.
    • Other Affiliation: Helmholtz Zentrum München
  • Wang, L.
    • Other Affiliation: Washington University School of Medicine
  • Wang, Y.X.
    • Other Affiliation: Capital Medical University
  • Wei, W.B.
    • Other Affiliation: Capital Medical University
  • Williams, C.
    • Other Affiliation: Washington University School of Medicine
  • Yao, J.
    • Other Affiliation: LABioMed at Harbor-UCLA Medical Center
  • Yu, C.
    • Other Affiliation: Huazhong University of Science and Technology
  • Yuan, J.-M.
    • Other Affiliation: University of Pittsburgh
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    • Other Affiliation: University of Michigan
  • Zonderman, A.B.
    • Other Affiliation: National Institutes of Health
  • Becker, D.M.
    • Other Affiliation: Johns Hopkins University School of Medicine
  • Boehnke, M.
    • Other Affiliation: University of Michigan
  • Bowden, D.W.
    • Other Affiliation: Wake Forest School of Medicine
  • Chambers, J.C.
    • Other Affiliation: Imperial College London
  • Deary, I.J.
    • Other Affiliation: University of Edinburgh
  • Esko, T.
    • Other Affiliation: University of Tartu
  • Farrall, M.
    • Other Affiliation: University of Oxford
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    • Other Affiliation: Skåne University Hospital
  • Freedman, B.I.
    • Other Affiliation: Wake Forest School of Medicine
  • Froguel, P.
    • Other Affiliation: European Genomic Institute for Dia
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.
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  • Article
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  • CC0 1.0 Universal
Journal title
  • PLoS ONE
Journal volume
  • 13
Journal issue
  • 6
Language
  • English
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  • Publisher

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