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, Desrivieres, 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-Proenca, Christine, Chambers, John C., Clarke, Toni-Kim, Dahmen, Norbert, de Geus, Eco J., Dick, Danielle, Ducci, Francesca, Easton, Alanna, Edenberg, Howard J., Esko, Tõnu, Fernandez-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., Nunez, 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, Tonjes, 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 and 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: 7119-7124. doi:10.1073/pnas.1017288108


Author Schumann, Gunter
Coin, Lachlan J.
Lourdusamy, Anbarasu
Charoen, Pimphen
Berger, Karen H.
Stacey, David
Desrivieres, 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-Proenca, Christine
Chambers, John C.
Clarke, Toni-Kim
Dahmen, Norbert
de Geus, Eco J.
Dick, Danielle
Ducci, Francesca
Easton, Alanna
Edenberg, Howard J.
Esko, Tõnu
Fernandez-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.
Nunez, 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
Tonjes, 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
Title Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2011-04-26
Year available 2011
Sub-type Article (original research)
DOI 10.1073/pnas.1017288108
Open Access Status Not yet assessed
Volume 108
Issue 17
Start page 7119
End page 7124
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
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 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 Epidemiologic
Genome-wide analysis
Transcriptional expression analysis
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HEALTH-F4-2007-201413
93558
01GS08152
FIS PI021570
SA044A08
RD06/0020/000
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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