Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
Schumann, Gunter;
Coin, Lachlan J;
Lourdusamy, Anbarasu;
Charoen, Pimphen;
Berger, Karen H;
Stacey, David;
Desrivières, Sylvane;
Aliev, Fazil A;
Khan, Anokhi A;
Amin, Najaf;
+106 more...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, Tõnu;
Fernández-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;
Tönjes, 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;
(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: https://doi.org/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.
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