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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.* ; Aschard, H.* ; Bartz, T.M.* ; Bielak, L.F.* ; Dorajoo, R.* ; Fisher, V.A.* ; Hartwig, F.P.* ; Horimoto, A.R.V.R.* ; Lohman, K.K.* ; Manning, A.K.* ; Rankinen, T.* ; Smith, A.V.* ; Tajuddin, S.M.* ; Wojczynski, M.K.* ; Alver, M.* ; Boissel, M.* ; Cai, Q.* ; Campbell, A.* ; Chai, J.F.* ; Chen, X.* ; Divers, J.* ; Gao, C.* ; Goel, A.* ; Hagemeijer, Y.* ; Harris, S.E.* ; He, M.* ; Hsu, F.C.* ; Jackson, A.U.* ; Kähönen, M.* ; Kasturiratne, A.* ; Komulainen, P.* ; Kühnel, B. ; Laguzzi, F.* ; Luan, J.* ; Matoba, N.* ; Nolte, I.M.* ; Padmanabhan, S.* ; Riaz, M.* ; Rueedi, R.* ; Robino, A.* ; Said, M.A.* ; Scott, R.A.* ; Sofer, T.* ; Stancáková, A.* ; Takeuchi, F.* ; Tayo, B.O.* ; van der Most, P.J.* ; Varga, T.V.* ; Vitart, V.* ; Meitinger, T. ; Peters, A. ; Strauch, K. ; Province, M.A.* ; Wen, W.* ; Yanek, L.R.* ; Zhang, W.* ; Zhao, J.H.* ; Afaq, S.* ; Amin, N.* ; Amini, M.* ; Arking, D.E.* ; Aung, T.* ; Boerwinkle, E.* ; Waldenberger, M. ; Levy, D.*

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

PLoS ONE 13:e0198166 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 approximate to 131 K 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 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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association; Body-mass Index; Transcription Factor Gata4; Environment Interaction; Hepatocellular-carcinoma; Ptp4a1-phf3-eys Variants; Functional Variation; Common Variants; Dependence; Loci
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 13, Issue: 6, Pages: , Article Number: e0198166 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)