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Schumann, G.* ; Coin, L.J.* ; Lourdusamy, A.* ; Charoen, P.* ; Berger, K.H.* ; Stacey, D.* ; Desrivières, S.* ; Aliev, F.A.* ; Khan, A.A.* ; Amin, N.* ; Aulchenko, Y.S.* ; Bakalkin, G.* ; Bakker, S.J.* ; Balkau, B.* ; Beulens, J.W.* ; Bilbao, A.* ; de Boer, R.A.* ; Beury, D.* ; Bots, M.L.* ; Breetvelt, E.J.* ; Cauchi, S.* ; Cavalcanti-Proença, C.* ; Chambers, J.C.* ; Clarke, T.K.* ; Dahmen, N.* ; de Geus, E.J.* ; Dick, D.* ; Ducci, F.* ; Easton, A.* ; Edenberg, H.J.* ; Esko, T.* ; Fernández-Medarde, A.* ; Foroud, T.* ; Freimer, N.B.* ; Girault, J.A.* ; Grobbee, DE.* ; Guarrera, S.* ; Gudbjartsson, D.F.* ; Hartikainen, A.L.* ; Heath, A.C.* ; Hesselbrock, V.* ; Hofman, A.* ; Hottenga, J.J.* ; Isohanni, M.K.* ; Kaprio, J.* ; Khaw, K.T.* ; Kuehnel, B. ; Laitinen, J.* ; Lobbens, S.* ; Luan, J.* ; Mangino, M.* ; Maroteaux, M.* ; Matullo, G.* ; McCarthy, M.I.* ; Mueller, C.* ; Navis, G.* ; Numans, M.E.* ; Núñez, A.* ; Nyholt, D.R.* ; Onland-Moret, C.N.* ; Oostra, B.A.* ; O'Reilly, P.F.* ; Palkovits, M.* ; Penninx, B.W.* ; Polidoro, S.* ; Pouta, A.* ; Prokopenko, I.* ; Ricceri, F.* ; Santos, E.* ; Smit, J.H.* ; Soranzo, N.* ; Song, K.* ; Sovio, U.* ; Stumvoll, M.* ; Surakk, I.* ; Thorgeirsson, TE.* ; Thorsteinsdottir, U.* ; Troakes, C.* ; Tyrfingsson, T.* ; Tönjes, A.* ; Uiterwaal, C.S.* ; Uitterlinden, A.G.* ; van der Harst, P.* ; van der Schouw, Y.T.* ; Staehlin, O.* ; Vogelzangs, N.* ; Vollenweider, P.* ; Waeber, G.* ; Wareham, N.J.* ; Waterworth, D.M.* ; Whitfield, J.B.* ; Wichmann, H.-E. ; Willemsen, G.* ; Witteman, J.C.* ; Yuan, X.* ; Zhai, G.* ; Zhao, J.H.* ; Zhang, W.* ; Martin, N.G.* ; Metspalu, A.* ; Döring, A. ; Scott, J.* ; Spector, T.D.* ; Loos, R.J.* ; Boomsma, D.I.* ; Mooser, V.* ; Peltonen, L.* ; Stefansson, K.* ; van Duijn, C.M.* ; Vineis, P.* ; Sommer, W.H.* ; Kooner, J.S.* ; Spanagel, R.* ; Heberlein, U.A.* ; Jarvelin, M.R.* ; Elliott, P.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Proc. Natl. Acad. Sci. U.S.A. 108, 7119-7124 (2011)
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Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
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Publication type Article: Journal article
Document type Scientific Article
Keywords genome-wide analysis; epidemiologic; transcriptional expression analysis
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 108, Issue: 17, Pages: 7119-7124 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington, USA
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-503900-001
PubMed ID 21471458
DOI 10.1073/pnas.1017288108
Scopus ID 79955569025
Erfassungsdatum 2011-06-20
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