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1 Publications

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    Heberlein Lab
    04/26/11 | Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
    Schumann G, Coin LJ, Lourdusamy A, Charoen P, Berger KH, Stacey D, Desrivières S, Aliev FA, Khan AA, Amin N, Aulchenko YS, Bakalkin G, Bakker SJ, Balkau B, Beulens JW, Bilbao A, de Boer RA, Beury D, Bots ML, Breetvelt EJ, Cauchi S, Cavalcanti-Proença C, Chambers JC, Clarke T, Dahmen N, de Geus EJ, Dick D, Ducci F, Easton A, Edenberg HJ, Esko T, Esk T, Fernández-Medarde A, Foroud T, Freimer NB, Girault J, Grobbee DE, Guarrera S, Gudbjartsson DF, Hartikainen A, Heath AC, Hesselbrock V, Hofman A, Hottenga J, Isohanni MK, Kaprio J, Khaw K, Kuehnel B, Laitinen J, Lobbens S, Luan J, Mangino M, Maroteaux M, Matullo G, McCarthy MI, Mueller C, Navis G, Numans ME, Núñez A, Nyholt DR, Onland-Moret CN, Oostra BA, O'Reilly PF, Palkovits M, Penninx BW, Polidoro S, Pouta A, Prokopenko I, Ricceri F, Santos E, Smit JH, Soranzo N, Song K, Sovio U, Stumvoll M, Surakk I, Thorgeirsson TE, Thorsteinsdottir U, Troakes C, Tyrfingsson T, Tönjes A, Uiterwaal CS, Uitterlinden AG, van der Harst P, van der Schouw YT, Staehlin O, Vogelzangs N, Vollenweider P, Waeber G, Wareham NJ, Waterworth DM, Whitfield JB, Wichmann EH, Willemsen G, Witteman JC, Yuan X, Zhai G, Zhao JH, Zhang W, Martin NG, Metspalu A, Doering A, Scott J, Spector TD, Loos RJ, Boomsma DI, Mooser V, Peltonen L, Stefansson K, van Duijn CM, Vineis P, Sommer WH, Kooner JS, Spanagel R, Heberlein UA, Jarvelin M, Elliott P
    Proceedings of the National Academy of Sciences of the United States of America. 2011 Apr 26;108(17):7119-24. doi: 10.1073/pnas.1017288108

    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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