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

GunterSchumann; Lachlan JCoin; AnbarasuLourdusamy; PimphenCharoen; Karen HBerger; DavidStacey; SylvaneDesrivières; Fazil AAliev; Anokhi AKhan; NajafAmin; +106 more... Yurii SAulchenko; GeorgyBakalkin; Stephan JBakker; BeverleyBalkau; Joline WBeulens; AinhoaBilbao; Rudolf Ade Boer; DelphineBeury; Michiel LBots; Elemi JBreetvelt; StéphaneCauchi; ChristineCavalcanti-Proença; John CChambers; Toni-KimClarke; NorbertDahmen; Eco Jde Geus; DanielleDick; FrancescaDucci; AlannaEaston; Howard JEdenberg; TõnuEsko; AlbertoFernández-Medarde; TatianaForoud; Nelson BFreimer; Jean-AntoineGirault; Diederick EGrobbee; SimonettaGuarrera; Daniel FGudbjartsson; Anna-LiisaHartikainen; Andrew CHeath; VictorHesselbrock; AlbertHofman; Jouke-JanHottenga; Matti KIsohanni; JaakkoKaprio; Kay-TeeKhaw; BrigitteKuehnel; JaanaLaitinen; StéphaneLobbens; Jian'anLuan; MassimoMangino; MatthieuMaroteaux; GiuseppeMatullo; Mark IMcCarthy; ChristianMueller; GerjanNavis; Mattijs ENumans; AlejandroNúñez; Dale RNyholt; Charlotte NOnland-Moret; Ben AOostra; Paul FO'Reilly; MiklosPalkovits; Brenda WPenninx; SilviaPolidoro; AnneliPouta; IngaProkopenko; FulvioRicceri; EugenioSantos; Johannes HSmit; NicoleSoranzo; KijoungSong; UllaSovio; MichaelStumvoll; IdaSurakk; Thorgeir EThorgeirsson; UnnurThorsteinsdottir; ClaireTroakes; ThorarinnTyrfingsson; AnkeTönjes; Cuno SUiterwaal; Andre GUitterlinden; Pimvan der Harst; Yvonne Tvan der Schouw; OliverStaehlin; NicoleVogelzangs; PeterVollenweider; GerardWaeber; Nicholas JWareham; Dawn MWaterworth; John BWhitfield; Erich HWichmann; GonnekeWillemsen; Jacqueline CWitteman; XinYuan; GuangjuZhai; Jing HZhao; WeihuaZhang; Nicholas GMartin; AndresMetspalu; AngelaDoering; JamesScott; Tim DSpector; Ruth JLoos; Dorret IBoomsma; VincentMooser; LeenaPeltonen; KariStefansson; Cornelia Mvan Duijn; PaoloVineis; Wolfgang HSommer; Jaspal SKooner; RainerSpanagel; Ulrike AHeberlein; Marjo-RiittaJarvelin; PaulElliott; (2011) Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proceedings of the National Academy of Sciences of the United States of America, 108 (17). pp. 7119-7124. ISSN 0027-8424 DOI: 10.1073/pnas.1017288108
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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.
Item Type Article
ISI 289888500082

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