Publication: Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
Issued Date
2011-04-26
Resource Type
ISSN
10916490
00278424
00278424
Other identifier(s)
2-s2.0-79955569025
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Proceedings of the National Academy of Sciences of the United States of America. Vol.108, No.17 (2011), 7119-7124
Suggested Citation
Gunter Schumann, Lachlan J. Coin, Anbarasu Lourdusamy, Pimphen Charoen, Karen H. Berger, David Stacey, Sylvane Desrivières, Fazil A. Aliev, Anokhi A. Khan, Najaf Amin, Yurii S. Aulchenko, Georgy Bakalkin, Stephan J. Bakker, Beverley Balkau, Joline W. Beulens, Ainhoa Bilbao, Rudolf A. De Boer, Delphine Beury, Michiel L. Bots, Elemi J. Breetvelt, Stéphane Cauchi, Christine Cavalcanti-Proença, John C. Chambers, Toni Kim Clarke, Norbert Dahmen, Eco J. De Geus, Danielle Dick, Francesca Ducci, Alanna Easton, Howard J. Edenberg, Tõnu Esk, Alberto Fernández-Medarde, Tatiana Foroud, Nelson B. Freimer, Jean Antoine Girault, Diederick E. Grobbee, Simonetta Guarrera, Daniel F. Gudbjartsson, Anna Liisa Hartikainen, Andrew C. Heath, Victor Hesselbrock, Albert Hofman, Jouke Jan Hottenga, Matti K. Isohanni, Jaakko Kaprio, Kay Tee Khaw, Brigitte Kuehnel, Jaana Laitinen, Stéphane Lobbens, Jian'an Luan, Massimo Mangino, Matthieu Maroteaux, Giuseppe Matullo, Mark I. McCarthy, Christian Mueller, Gerjan Navis, Mattijs E. Numans, Alejandro Núñez, Dale R. Nyholt, Charlotte N. Onland-Moret, Ben A. Oostra, Paul F. O'Reilly, Miklos Palkovits, Brenda W. Penninx, Silvia Polidoro, Anneli Pouta, Inga Prokopenko, Fulvio Ricceri, Eugenio Santos, Johannes H. Smit, Nicole Soranzo, Kijoung Song, Ulla Sovio, Michael Stumvoll, Ida Surakk, Thorgeir E. Thorgeirsson, Unnur Thorsteinsdottir, Claire Troakes, Thorarinn Tyrfingsson, Anke Tönjes, Cuno S. Uiterwaal, Andre G. Uitterlinden, Pim Van Der Harst, Yvonne T. Van Der Schouw 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. Vol.108, No.17 (2011), 7119-7124. doi:10.1073/pnas.1017288108 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/12920
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Title
Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
Author(s)
Gunter Schumann
Lachlan J. Coin
Anbarasu Lourdusamy
Pimphen Charoen
Karen H. Berger
David Stacey
Sylvane Desrivières
Fazil A. Aliev
Anokhi A. Khan
Najaf Amin
Yurii S. Aulchenko
Georgy Bakalkin
Stephan J. Bakker
Beverley Balkau
Joline W. Beulens
Ainhoa Bilbao
Rudolf A. De Boer
Delphine Beury
Michiel L. Bots
Elemi J. Breetvelt
Stéphane Cauchi
Christine Cavalcanti-Proença
John C. Chambers
Toni Kim Clarke
Norbert Dahmen
Eco J. De Geus
Danielle Dick
Francesca Ducci
Alanna Easton
Howard J. Edenberg
Tõnu Esk
Alberto Fernández-Medarde
Tatiana Foroud
Nelson B. Freimer
Jean Antoine Girault
Diederick E. Grobbee
Simonetta Guarrera
Daniel F. Gudbjartsson
Anna Liisa Hartikainen
Andrew C. Heath
Victor Hesselbrock
Albert Hofman
Jouke Jan Hottenga
Matti K. Isohanni
Jaakko Kaprio
Kay Tee Khaw
Brigitte Kuehnel
Jaana Laitinen
Stéphane Lobbens
Jian'an Luan
Massimo Mangino
Matthieu Maroteaux
Giuseppe Matullo
Mark I. McCarthy
Christian Mueller
Gerjan Navis
Mattijs E. Numans
Alejandro Núñez
Dale R. Nyholt
Charlotte N. Onland-Moret
Ben A. Oostra
Paul F. O'Reilly
Miklos Palkovits
Brenda W. Penninx
Silvia Polidoro
Anneli Pouta
Inga Prokopenko
Fulvio Ricceri
Eugenio Santos
Johannes H. Smit
Nicole Soranzo
Kijoung Song
Ulla Sovio
Michael Stumvoll
Ida Surakk
Thorgeir E. Thorgeirsson
Unnur Thorsteinsdottir
Claire Troakes
Thorarinn Tyrfingsson
Anke Tönjes
Cuno S. Uiterwaal
Andre G. Uitterlinden
Pim Van Der Harst
Yvonne T. Van Der Schouw
Lachlan J. Coin
Anbarasu Lourdusamy
Pimphen Charoen
Karen H. Berger
David Stacey
Sylvane Desrivières
Fazil A. Aliev
Anokhi A. Khan
Najaf Amin
Yurii S. Aulchenko
Georgy Bakalkin
Stephan J. Bakker
Beverley Balkau
Joline W. Beulens
Ainhoa Bilbao
Rudolf A. De Boer
Delphine Beury
Michiel L. Bots
Elemi J. Breetvelt
Stéphane Cauchi
Christine Cavalcanti-Proença
John C. Chambers
Toni Kim Clarke
Norbert Dahmen
Eco J. De Geus
Danielle Dick
Francesca Ducci
Alanna Easton
Howard J. Edenberg
Tõnu Esk
Alberto Fernández-Medarde
Tatiana Foroud
Nelson B. Freimer
Jean Antoine Girault
Diederick E. Grobbee
Simonetta Guarrera
Daniel F. Gudbjartsson
Anna Liisa Hartikainen
Andrew C. Heath
Victor Hesselbrock
Albert Hofman
Jouke Jan Hottenga
Matti K. Isohanni
Jaakko Kaprio
Kay Tee Khaw
Brigitte Kuehnel
Jaana Laitinen
Stéphane Lobbens
Jian'an Luan
Massimo Mangino
Matthieu Maroteaux
Giuseppe Matullo
Mark I. McCarthy
Christian Mueller
Gerjan Navis
Mattijs E. Numans
Alejandro Núñez
Dale R. Nyholt
Charlotte N. Onland-Moret
Ben A. Oostra
Paul F. O'Reilly
Miklos Palkovits
Brenda W. Penninx
Silvia Polidoro
Anneli Pouta
Inga Prokopenko
Fulvio Ricceri
Eugenio Santos
Johannes H. Smit
Nicole Soranzo
Kijoung Song
Ulla Sovio
Michael Stumvoll
Ida Surakk
Thorgeir E. Thorgeirsson
Unnur Thorsteinsdottir
Claire Troakes
Thorarinn Tyrfingsson
Anke Tönjes
Cuno S. Uiterwaal
Andre G. Uitterlinden
Pim Van Der Harst
Yvonne T. Van Der Schouw
Other Contributor(s)
King's College London
Imperial College London
Mahidol University
National Health Service
Ernest Gallo Clinic and Research Center
Virginia Commonwealth University
Erasmus University Medical Center
Uppsala Universitet
University of Groningen, University Medical Center Groningen
Inserm
Universite Paris-Sud XI
University Medical Center Utrecht
Zentralinstitut fur Seelische Gesundheit
CNRS Centre National de la Recherche Scientifique
Johannes Gutenberg Universitat Mainz
Indiana University-Purdue University Indianapolis
University of Tartu
Estonian Biocentre
Universidad de Salamanca
Jane & Terry Semel Institute for Neuroscience & Human Behavior
Universite Pierre et Marie Curie
Institute for Scientific Interchange Foundation
University of Iceland
Oulun Yliopisto
Washington University in St. Louis, School of Medicine
University of Connecticut
VU University Medical Center
Helsingin Yliopisto
National Institute for Health and Welfare
Institute for Molecular Medicine
University of Cambridge
Helmholtz Center Munich German Research Center for Environmental Health
Tyoterveyslaitos
Medical Research Council
Universita degli Studi di Torino
University of Oxford
Friedrich-Alexander-Universität Erlangen-Nürnberg
Queensland Institute of Medical Research
Semmelweis Egyetem
Institute for Research in Extramural Medicine - EMGO
Leiden University Medical Center - LUMC
Wellcome Trust Centre for Human Genetics
Wellcome Trust Sanger Institute
GlaxoSmithKline
Universitat Leipzig
Vogur Samtök Áhugafólks um Áfengis Addiction Treatment Center
Centre Hospitalier Universitaire Vaudois
Ludwig-Maximilians-Universitat Munchen
Klinikum der Universitat Munchen
Hammersmith Hospital
Health Protection Agency
Imperial College London
Mahidol University
National Health Service
Ernest Gallo Clinic and Research Center
Virginia Commonwealth University
Erasmus University Medical Center
Uppsala Universitet
University of Groningen, University Medical Center Groningen
Inserm
Universite Paris-Sud XI
University Medical Center Utrecht
Zentralinstitut fur Seelische Gesundheit
CNRS Centre National de la Recherche Scientifique
Johannes Gutenberg Universitat Mainz
Indiana University-Purdue University Indianapolis
University of Tartu
Estonian Biocentre
Universidad de Salamanca
Jane & Terry Semel Institute for Neuroscience & Human Behavior
Universite Pierre et Marie Curie
Institute for Scientific Interchange Foundation
University of Iceland
Oulun Yliopisto
Washington University in St. Louis, School of Medicine
University of Connecticut
VU University Medical Center
Helsingin Yliopisto
National Institute for Health and Welfare
Institute for Molecular Medicine
University of Cambridge
Helmholtz Center Munich German Research Center for Environmental Health
Tyoterveyslaitos
Medical Research Council
Universita degli Studi di Torino
University of Oxford
Friedrich-Alexander-Universität Erlangen-Nürnberg
Queensland Institute of Medical Research
Semmelweis Egyetem
Institute for Research in Extramural Medicine - EMGO
Leiden University Medical Center - LUMC
Wellcome Trust Centre for Human Genetics
Wellcome Trust Sanger Institute
GlaxoSmithKline
Universitat Leipzig
Vogur Samtök Áhugafólks um Áfengis Addiction Treatment Center
Centre Hospitalier Universitaire Vaudois
Ludwig-Maximilians-Universitat Munchen
Klinikum der Universitat Munchen
Hammersmith Hospital
Health Protection Agency
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 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.