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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 (author)
Coin, Lachlan J. (author)
Lourdusamy, Anbarasu (author)
show more...
Charoen, Pimphen (author)
Berger, Karen H. (author)
Stacey, David (author)
Desrivieres, Sylvane (author)
Aliev, Fazil A. (author)
Khan, Anokhi A. (author)
Amin, Najaf (author)
Aulchenko, Yurii S. (author)
Bakalkin, Georgy (author)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap
Bakker, Stephan J. (author)
Balkau, Beverley (author)
Beulens, Joline W. (author)
Bilbao, Ainhoa (author)
de Boer, Rudolf A. (author)
Beury, Delphine (author)
Bots, Michiel L. (author)
Breetvelt, Elemi J. (author)
Cauchi, Stephane (author)
Cavalcanti-Proenca, Christine (author)
Chambers, John C. (author)
Clarke, Toni-Kim (author)
Dahmen, Norbert (author)
de Geus, Eco J. (author)
Dick, Danielle (author)
Ducci, Francesca (author)
Easton, Alanna (author)
Edenberg, Howard J. (author)
Esk, Tonu (author)
Fernandez-Medarde, Alberto (author)
Foroud, Tatiana (author)
Freimer, Nelson B. (author)
Girault, Jean-Antoine (author)
Grobbee, Diederick E. (author)
Guarrera, Simonetta (author)
Gudbjartsson, Daniel F. (author)
Hartikainen, Anna-Liisa (author)
Heath, Andrew C. (author)
Hesselbrock, Victor (author)
Hofman, Albert (author)
Hottenga, Jouke-Jan (author)
Isohanni, Matti K. (author)
Kaprio, Jaakko (author)
Khaw, Kay-Tee (author)
Kuehnel, Brigitte (author)
Laitinen, Jaana (author)
Lobbens, Stephane (author)
Luan, Jian'an (author)
Mangino, Massimo (author)
Maroteaux, Matthieu (author)
Matullo, Giuseppe (author)
McCarthy, Mark I. (author)
Mueller, Christian (author)
Navis, Gerjan (author)
Numans, Mattijs E. (author)
Nunez, Alejandro (author)
Nyholt, Dale R. (author)
Onland-Moret, Charlotte N. (author)
Oostra, Ben A. (author)
O'Reilly, Paul F. (author)
Palkovits, Miklos (author)
Penninx, Brenda W. (author)
Polidoro, Silvia (author)
Pouta, Anneli (author)
Prokopenko, Inga (author)
Ricceri, Fulvio (author)
Santos, Eugenio (author)
Smit, Johannes H. (author)
Soranzo, Nicole (author)
Song, Kijoung (author)
Sovio, Ulla (author)
Stumvoll, Michael (author)
Surakk, Ida (author)
Thorgeirsson, Thorgeir E. (author)
Thorsteinsdottir, Unnur (author)
Troakes, Claire (author)
Tyrfingsson, Thorarinn (author)
Toenjes, Anke (author)
Uiterwaal, Cuno S. (author)
Uitterlinden, Andre G. (author)
van der Harst, Pim (author)
van der Schouw, Yvonne T. (author)
Staehlin, Oliver (author)
Vogelzangs, Nicole (author)
Vollenweider, Peter (author)
Waeber, Gerard (author)
Wareham, Nicholas J. (author)
Waterworth, Dawn M. (author)
Whitfield, John B. (author)
Wichmann, Erich H. (author)
Willemsen, Gonneke (author)
Witteman, Jacqueline C. (author)
Yuan, Xin (author)
Zhai, Guangju (author)
Zhao, Jing H. (author)
Zhang, Weihua (author)
Martin, Nicholas G. (author)
Metspalu, Andres (author)
Doering, Angela (author)
Scott, James (author)
Spector, Tim D. (author)
Loos, Ruth J. (author)
Boomsma, Dorret I. (author)
Mooser, Vincent (author)
Peltonen, Leena (author)
Stefansson, Kari (author)
van Duijn, Cornelia M. (author)
Vineis, Paolo (author)
Sommer, Wolfgang H. (author)
Kooner, Jaspal S. (author)
Spanagel, Rainer (author)
Heberlein, Ulrike A. (author)
Jarvelin, Marjo-Riitta (author)
Elliott, Paul (author)
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 (creator_code:org_t)
2011-04-06
2011
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:17, s. 7119-7124
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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 similar to 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 x 10(-8) to P = 4 x 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. Downregulation 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.

Keyword

genome-wide analysis
epidemiologic
transcriptional expression analysis
MEDICINE
MEDICIN

Publication and Content Type

ref (subject category)
art (subject category)

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By the author/editor
Schumann, Gunter
Coin, Lachlan J.
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Charoen, Pimphen
Berger, Karen H.
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Khan, Anokhi A.
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Toenjes, Anke
Uiterwaal, Cuno ...
Uitterlinden, An ...
van der Harst, P ...
van der Schouw, ...
Staehlin, Oliver
Vogelzangs, Nico ...
Vollenweider, Pe ...
Waeber, Gerard
Wareham, Nichola ...
Waterworth, Dawn ...
Whitfield, John ...
Wichmann, Erich ...
Willemsen, Gonne ...
Witteman, Jacque ...
Yuan, Xin
Zhai, Guangju
Zhao, Jing H.
Zhang, Weihua
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Metspalu, Andres
Doering, Angela
Scott, James
Spector, Tim D.
Loos, Ruth J.
Boomsma, Dorret ...
Mooser, Vincent
Peltonen, Leena
Stefansson, Kari
van Duijn, Corne ...
Vineis, Paolo
Sommer, Wolfgang ...
Kooner, Jaspal S ...
Spanagel, Rainer
Heberlein, Ulrik ...
Jarvelin, Marjo- ...
Elliott, Paul
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Proceedings of t ...
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Uppsala University

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