Genome-wide association and genetic functional studies identify
autism susceptibility candidate 2
gene (
AUTS2
) in the regulation of alcohol consumption
Authors: 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 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 
Published: April 2011

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.