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


ABSTRACT: 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.

SUBMITTER: Schumann G 

PROVIDER: S-EPMC3084048 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Schumann Gunter G   Coin Lachlan J LJ   Lourdusamy Anbarasu A   Charoen Pimphen P   Berger Karen H KH   Stacey David D   Desrivières Sylvane S   Aliev Fazil A FA   Khan Anokhi A AA   Amin Najaf N   Aulchenko Yurii S YS   Bakalkin Georgy G   Bakker Stephan J SJ   Balkau Beverley B   Beulens Joline W JW   Bilbao Ainhoa A   de Boer Rudolf A RA   Beury Delphine D   Bots Michiel L ML   Breetvelt Elemi J EJ   Cauchi Stéphane S   Cavalcanti-Proença Christine C   Chambers John C JC   Clarke Toni-Kim TK   Dahmen Norbert N   de Geus Eco J EJ   Dick Danielle D   Ducci Francesca F   Easton Alanna A   Edenberg Howard J HJ   Esko Tõnu T   Fernández-Medarde Alberto A   Foroud Tatiana T   Freimer Nelson B NB   Girault Jean-Antoine JA   Grobbee Diederick E DE   Guarrera Simonetta S   Gudbjartsson Daniel F DF   Hartikainen Anna-Liisa AL   Heath Andrew C AC   Hesselbrock Victor V   Hofman Albert A   Hottenga Jouke-Jan JJ   Isohanni Matti K MK   Kaprio Jaakko J   Khaw Kay-Tee KT   Kuehnel Brigitte B   Laitinen Jaana J   Lobbens Stéphane S   Luan Jian'an J   Mangino Massimo M   Maroteaux Matthieu M   Matullo Giuseppe G   McCarthy Mark I MI   Mueller Christian C   Navis Gerjan G   Numans Mattijs E ME   Núñez Alejandro A   Nyholt Dale R DR   Onland-Moret Charlotte N CN   Oostra Ben A BA   O'Reilly Paul F PF   Palkovits Miklos M   Penninx Brenda W BW   Polidoro Silvia S   Pouta Anneli A   Prokopenko Inga I   Ricceri Fulvio F   Santos Eugenio E   Smit Johannes H JH   Soranzo Nicole N   Song Kijoung K   Sovio Ulla U   Stumvoll Michael M   Surakk Ida I   Thorgeirsson Thorgeir E TE   Thorsteinsdottir Unnur U   Troakes Claire C   Tyrfingsson Thorarinn T   Tönjes Anke A   Uiterwaal Cuno S CS   Uitterlinden Andre G AG   van der Harst Pim P   van der Schouw Yvonne T YT   Staehlin Oliver O   Vogelzangs Nicole N   Vollenweider Peter P   Waeber Gerard G   Wareham Nicholas J NJ   Waterworth Dawn M DM   Whitfield John B JB   Wichmann Erich H EH   Willemsen Gonneke G   Witteman Jacqueline C JC   Yuan Xin X   Zhai Guangju G   Zhao Jing H JH   Zhang Weihua W   Martin Nicholas G NG   Metspalu Andres A   Doering Angela A   Scott James J   Spector Tim D TD   Loos Ruth J RJ   Boomsma Dorret I DI   Mooser Vincent V   Peltonen Leena L   Stefansson Kari K   van Duijn Cornelia M CM   Vineis Paolo P   Sommer Wolfgang H WH   Kooner Jaspal S JS   Spanagel Rainer R   Heberlein Ulrike A UA   Jarvelin Marjo-Riitta MR   Elliott Paul P  

Proceedings of the National Academy of Sciences of the United States of America 20110406 17


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 s  ...[more]

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