Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
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- Schumann, Gunter; Coin, Lachlan J; Lourdusamy, Anbarasu; Charoen, Pimphen; Berger, Karen H; Stacey, David; Desrivières, Sylvane; Aliev, Fazil A; Khan, Anokhi A; Amin, Najaf; Aulchenko, Yurii S; Bakalkin, Georgy; Bakker, Stephan J; Balkau, Beverley; Beulens, Joline W; Bilbao, Ainhoa; de Boer, Rudolf A; Beury, Delphine; Bots, Michiel L; Breetvelt, Elemi J; Cauchi, Stéphane; Cavalcanti-Proença, Christine; Chambers, John C; Clarke, Toni-Kim; Dahmen, Norbert; de Geus, Eco J; Dick, Danielle; Ducci, Francesca; Easton, Alanna; Edenberg, Howard J; Esko, Tánu; FernÑndez-Medarde, Alberto; Foroud, Tatiana; Freimer, Nelson B; Girault, Jean-Antoine; Grobbee, Diederick E; Guarrera, Simonetta; Gudbjartsson, Daniel F; Hartikainen, Anna-Liisa; Heath, Andrew C; Hesselbrock, Victor; Hofman, Albert; Hottenga, Jouke-Jan; Isohanni, Matti K; Kaprio, Jaakko; Khaw, Kay-Tee; Kuehnel, Brigitte; Laitinen, Jaana; Lobbens, Stéphane; Luan, Jian'an; Mangino, Massimo; Maroteaux, Matthieu; Matullo, Giuseppe; McCarthy, Mark I; Mueller, Christian; Navis, Gerjan; Numans, Mattijs E; Núñez, Alejandro; Nyholt, Dale R; Onland-Moret, Charlotte N; Oostra, Ben A; O'Reilly, Paul F; Palkovits, Miklos; Penninx, Brenda W; Polidoro, Silvia; Pouta, Anneli; Prokopenko, Inga; Ricceri, Fulvio; Santos, Eugenio; Smit, Johannes H; Soranzo, Nicole; Song, Kijoung; Sovio, Ulla; Stumvoll, Michael; Surakk, Ida; Thorgeirsson, Thorgeir E; Thorsteinsdottir, Unnur; Troakes, Claire; Tyrfingsson, Thorarinn; Tânjes, Anke; Uiterwaal, Cuno S; Uitterlinden, Andre G; van der Harst, Pim; van der Schouw, Yvonne T; Staehlin, Oliver; Vogelzangs, Nicole; Vollenweider, Peter; Waeber, Gerard; Wareham, Nicholas J; Waterworth, Dawn M; Whitfield, John B; Wichmann, Erich H; Willemsen, Gonneke; Witteman, Jacqueline C; Yuan, Xin; Zhai, Guangju; Zhao, Jing H; Zhang, Weihua; Martin, Nicholas G; Metspalu, Andres; Doering, Angela; Scott, James; Spector, Tim D; Loos, Ruth J; Boomsma, Dorret I; Mooser, Vincent; Peltonen, Leena; Stefansson, Kari; van Duijn, Cornelia M; Vineis, Paolo; Sommer, Wolfgang H; Kooner, Jaspal S; Spanagel, Rainer; Heberlein, Ulrike A; Jarvelin, Marjo-Riitta; Elliott, Paul
- Year
- 2011
- Journal
- Proceedings of the National Academy of Sciences of the United States of America
- PMID
- 21471458
- DOI
- 10.1073/pnas.1017288108
- PMCID
- PMC3084048
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 βΌ2.5 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 Γ 10(-8) to P = 4 Γ 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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