1. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
- Author
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Schumann, G. (Gunter), Coin, L. (Lachlan), Lourdusamy, A. (Anbarasu), Charoen, P. (Pimphen), Berger, K.H. (Karen), Stacey, D. (David), Desrivières, S. (Sylvane), Aliev, F.A. (Fazil), Khan, A.A. (Anokhi), Amin, N. (Najaf), Bakalkin, G. (Georgy), Balkau, B. (Beverley), Beulens, J.W.J. (Joline), Bilbao, A. (Ainhoa), Boer, R.A. (Rudolf) de, Beury, D. (Delphine), Bots, M.L. (Michiel), Breetvelt, E.J. (Elemi), Cauchi, S. (Stephane), Cavalcanti-Proença, C. (Christine), Chambers, J.C. (John), Clarke, T.-K., Dahmen, N. (N.), Geus, E.J.C. (Eco) de, Dick, D. (Danielle), Ducci, F. (Francesca), Easton, A. (Alanna), Edenberg, H.J. (Howard), Esk, T. (Tõnu), Fernández-Medarde, A. (Alberto), Foroud, T. (Tatiana), Freimer, N.B. (Nelson), Girault, J.-A., Grobbee, D.E. (Diederick), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Hartikainen, A.L., Heath, A.C. (Andrew), Hesselbrock, V. (Victor), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Isohanni, M.K. (Matti), Kaprio, J. (Jaakko), Khaw, K-T. (Kay-Tee), Kuehnel, B. (Brigitte), Laitinen, J. (Jaana), Lobbens, S. (Stéphane), Luan, J., Mangino, M. (Massimo), Maroteaux, M. (Matthieu), Matullo, G. (Giuseppe), McCarthy, M.I. (Mark), Mueller, C. (Christian), Navis, G. (Gerjan), Numans, M.E. (Mattijs), Núñez, A.M. (Alejandro), Nyholt, D.R. (Dale), Onland-Moret, N.C. (Charlotte), Oostra, B.A. (Ben), O'Reilly, P.F. (Paul), Palkovits, M. (Miklos), Penninx, B.W.J.H. (Brenda), Polidoro, S. (Silvia), Pouta, A. (Anneli), Prokopenko, I. (Inga), Ricceri, F. (Fulvio), Santos, E. (Eugenio), Smit, J.H. (Johannes), Soranzo, N. (Nicole), Song, K. (Kijoung), Sovio, U. (Ulla), Stumvoll, M. (Michael), Surakk, I. (Ida), Thorgeirsson, T.E. (Thorgeir), Thorsteinsdottir, U. (Unnur), Troakes, C. (Claire), Tyrfingsson, T. (Thorarinn), Tönjes, A. (Anke), Uiterwaal, C.S.P.M. (Cuno), Uitterlinden, A.G. (André), Harst, P. (Pim) van der, Schouw, Y.T. (Yvonne) van der, Staehlin, O. (Oliver), Vogelzangs, N. (Nicole), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Whitfield, J.B. (John), Wichmann, E.H. (Erich), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Yuan, X. (Xin), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zhang, W. (Weihua), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Doering, A. (Angela), Scott, J. (James), Spector, T.D. (Timothy), Loos, R.J.F. (Ruth), Boomsma, D.I. (Dorret), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Stefansson, K. (Kari), Tikka-Kleemola, P. (Päivi), Vineis, P. (Paolo), Sommer, W.H. (Wolfgang), Kooner, J.S. (Jaspal), Spanagel, R. (Rainer), Heberlein, U.A. (Ulrike), Järvelin, M.R., Elliott, P. (Paul), Aulchenko, Y.S. (Yurii), Bakker, S.J.L. (Stephan), Schumann, G. (Gunter), Coin, L. (Lachlan), Lourdusamy, A. (Anbarasu), Charoen, P. (Pimphen), Berger, K.H. (Karen), Stacey, D. (David), Desrivières, S. (Sylvane), Aliev, F.A. (Fazil), Khan, A.A. (Anokhi), Amin, N. (Najaf), Bakalkin, G. (Georgy), Balkau, B. (Beverley), Beulens, J.W.J. (Joline), Bilbao, A. (Ainhoa), Boer, R.A. (Rudolf) de, Beury, D. (Delphine), Bots, M.L. (Michiel), Breetvelt, E.J. (Elemi), Cauchi, S. (Stephane), Cavalcanti-Proença, C. (Christine), Chambers, J.C. (John), Clarke, T.-K., Dahmen, N. (N.), Geus, E.J.C. (Eco) de, Dick, D. (Danielle), Ducci, F. (Francesca), Easton, A. (Alanna), Edenberg, H.J. (Howard), Esk, T. (Tõnu), Fernández-Medarde, A. (Alberto), Foroud, T. (Tatiana), Freimer, N.B. (Nelson), Girault, J.-A., Grobbee, D.E. (Diederick), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Hartikainen, A.L., Heath, A.C. (Andrew), Hesselbrock, V. (Victor), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Isohanni, M.K. (Matti), Kaprio, J. (Jaakko), Khaw, K-T. (Kay-Tee), Kuehnel, B. (Brigitte), Laitinen, J. (Jaana), Lobbens, S. (Stéphane), Luan, J., Mangino, M. (Massimo), Maroteaux, M. (Matthieu), Matullo, G. (Giuseppe), McCarthy, M.I. (Mark), Mueller, C. (Christian), Navis, G. (Gerjan), Numans, M.E. (Mattijs), Núñez, A.M. (Alejandro), Nyholt, D.R. (Dale), Onland-Moret, N.C. (Charlotte), Oostra, B.A. (Ben), O'Reilly, P.F. (Paul), Palkovits, M. (Miklos), Penninx, B.W.J.H. (Brenda), Polidoro, S. (Silvia), Pouta, A. (Anneli), Prokopenko, I. (Inga), Ricceri, F. (Fulvio), Santos, E. (Eugenio), Smit, J.H. (Johannes), Soranzo, N. (Nicole), Song, K. (Kijoung), Sovio, U. (Ulla), Stumvoll, M. (Michael), Surakk, I. (Ida), Thorgeirsson, T.E. (Thorgeir), Thorsteinsdottir, U. (Unnur), Troakes, C. (Claire), Tyrfingsson, T. (Thorarinn), Tönjes, A. (Anke), Uiterwaal, C.S.P.M. (Cuno), Uitterlinden, A.G. (André), Harst, P. (Pim) van der, Schouw, Y.T. (Yvonne) van der, Staehlin, O. (Oliver), Vogelzangs, N. (Nicole), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Whitfield, J.B. (John), Wichmann, E.H. (Erich), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Yuan, X. (Xin), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zhang, W. (Weihua), Martin, N.G. (Nicholas), Metspalu, A. (Andres), Doering, A. (Angela), Scott, J. (James), Spector, T.D. (Timothy), Loos, R.J.F. (Ruth), Boomsma, D.I. (Dorret), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Stefansson, K. (Kari), Tikka-Kleemola, P. (Päivi), Vineis, P. (Paolo), Sommer, W.H. (Wolfgang), Kooner, J.S. (Jaspal), Spanagel, R. (Rainer), Heberlein, U.A. (Ulrike), Järvelin, M.R., Elliott, P. (Paul), Aulchenko, Y.S. (Yurii), and Bakker, S.J.L. (Stephan)
- Abstract
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 x 10-8to P = 4 x 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. Downregulation 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 mech
- Published
- 2011
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