Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene ( AUTS2 ) in the regulation of alcohol consumption
Open accessAbstract
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.
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The association of ADH1B with ALC and alcohol consumption was extended to European ancestry subjects using a candidate gene approach.
“Using a candidate gene approach, the association of ADH1B with ALC and alcohol consumption was extended to European ancestry subjects. 101”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [101]
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- Authors
- Schumann, G., Coin, L. J., Lourdusamy, A., Charoen, P., Berger, K. H., Stacey, D., Desrivières, S., Aliev, F. A., Khan, A. A., Amin, N., Aulchenko, Y. S., Bakalkin, G., Bakker, S. J., Balkau, B., Beulens, J. W., Bilbao, A., de Boer, R. A., Beury, D., Bots, M. L., Breetvelt, E. J., Cauchi, S., Cavalcanti-Proença, C., Chambers, J. C., Clarke, T.-K., Dahmen, N., de Geus, E. J., Dick, D., Ducci, F., Easton, A., Edenberg, H. J., Esko, T., Fernández-Medarde, A., Foroud, T., Freimer, N. B., Girault, J.-A., Grobbee, D. E., Guarrera, S., Gudbjartsson, D. F., Hartikainen, A.-L., Heath, A. C., Hesselbrock, V., Hofman, A., Hottenga, J.-J., Isohanni, M. K., Kaprio, J., Khaw, K.-T., Kuehnel, B., Laitinen, J., Lobbens, S., Luan, J., Mangino, M., Maroteaux, M., Matullo, G., McCarthy, M. I., Mueller, C., Navis, G., Numans, M. E., Núñez, A., Nyholt, D. R., Onland-Moret, C. N., Oostra, B. A., O'Reilly, P. F., Palkovits, M., Penninx, B. W., Polidoro, S., Pouta, A., Prokopenko, I., Ricceri, F., Santos, E., Smit, J. H., Soranzo, N., Song, K., Sovio, U., Stumvoll, M., Surakk, I., Thorgeirsson, T. E., Thorsteinsdottir, U., Troakes, C., Tyrfingsson, T., Tönjes, A., Uiterwaal, C. S., Uitterlinden, A. G., van der Harst, P., van der Schouw, Y. T., Staehlin, O., Vogelzangs, N., Vollenweider, P., Waeber, G., Wareham, N. J., Waterworth, D. M., Whitfield, J. B., Wichmann, E. H., Willemsen, G., Witteman, J. C., Yuan, X., Zhai, G., Zhao, J. H., Zhang, W., Martin, N. G., Metspalu, A., Doering, A., Scott, J., Spector, T. D., Loos, R. J., Boomsma, D. I., Mooser, V., Peltonen, L., Stefansson, K., van Duijn, C. M., Vineis, P., Sommer, W. H., Kooner, J. S., Spanagel, R., Heberlein, U. A., Jarvelin, M.-R., & Elliott, P.
- Affiliations
- Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London SE5 8AF, United Kingdom;
- Imperial College London (GB)
- King's College London (GB)
- Imperial College Healthcare NHS Trust (GB)
- University of California, San Francisco (US)
- Virginia Commonwealth University, Richmond, VA 23284;
- Erasmus MC (NL)
- Uppsala University (SE)
- University Medical Center Groningen (NL)
- Université Paris-Sud (FR)
- University Medical Center Utrecht (NL)
- Central Institute of Mental Health (DE)
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, The Netherlands;
- Centre National de la Recherche Scientifique (FR)
- Johannes Gutenberg University Mainz (DE)
- Indiana University, School of Medicine, Indianapolis, IN 46202-3082;
- Virginia Commonwealth University (US)
- Indiana University School of Medicine (US)
- Estonian Biocentre (EE)
- Comision de Investigaciones Cientificas de la Provincia de Buenos Aires-Instituto de Biología Molecular y Celular del Cáncer de Salamanca, University of Salamanca–Consejo Superior de Investigaciones Cientificas (Spain), 37007 Salamanca, Spain;
- University of California, Los Angeles (US)
- Inserm (FR)
- Institute for Scientific Interchange (IT)
- deCODE Genetics (Iceland) (IS)
- University of Oulu (FI)
- Washington University in St. Louis (US)
- University of Connecticut (US)
- Genetic Epidemiology Unit, Department of Epidemiology and Clinical Genetics, Erasmus University Medical Centre, Rotterdam 3000CA, The Netherlands;
- Vrije Universiteit Amsterdam (NL)
- University of Helsinki (FI)
- University of Cambridge (GB)
- Helmholtz Munich (DE)
- Finnish Institute of Occupational Health (FI)
- Wellcome/MRC Institute of Metabolic Science (GB)
- University of Turin (IT)
- University of Oxford (GB)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Consejo Superior de Investigaciones Científicas (ES)
- QIMR Berghofer Medical Research Institute (AU)
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3508 GA, The Netherlands;
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, United Kingdom;
- Semmelweiss University, H-1094, Budapest, Hungary;
- National Institute for Health and Welfare, FI-90101, Oulu, Finland;
- Centre for Human Genetics (GB)
- Amsterdam Public Health (NL)
- GlaxoSmithKline (United States) (US)
- Department of Medicine, University of Leipzig, 04103 Leipzig, Germany;
- Finnish Institute for Health and Welfare (FI)
- deCODE genetics, Faculty of Medicine, Reykjavik and University of Iceland, Reykjavik IS 101, Iceland;
- Vogur Samtök áhugafólks um áfengis Addiction Treatment Center, Reykjavik 112, Iceland;
- Leipzig University (DE)
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3015 CE, The Netherlands;
- Department of Medicine, Centre Hospitalier Universitaire Vaudois University Hospital, CH-1011 Lausanne, Switzerland;
- Hammersmith Hospital (GB)
- MRC Centre for Environment and Health (GB)
- ORCID
- Coin, Lachlan J.
- Lourdusamy, Anbarasu
- Charoen, Pimphen
- Stacey, David
- Desrivières, Sylvane
- Khan, Anokhi A.
- Amin, Najaf
- Aulchenko, Yurii S.
- Bakalkin, Georgy
- Bakker, Stephan J.
- Balkau, Beverley
- Beulens, Joline W.
- Bilbao, Ainhoa
- Beury, Delphine
- Bots, Michiel L.
- Breetvelt, Elemi J.
- Cauchi, Stéphane
- Chambers, John C.
- Clarke, Toni-Kim
- Dick, Danielle
- Edenberg, Howard J.
- Esko, Tõnu
- Foroud, Tatiana
- Girault, Jean-Antoine
- Grobbee, Diederick E.
- Guarrera, Simonetta
- Gudbjartsson, Daniel F.
- Heath, Andrew C.
- Hesselbrock, Victor
- Hottenga, Jouke-Jan
- Isohanni, Matti K.
- Kaprio, Jaakko
- Khaw, Kay-Tee
- Laitinen, Jaana
- Luan, Jian'an
- Mangino, Massimo
- Maroteaux, Matthieu
- Matullo, Giuseppe
- McCarthy, Mark I.
- Navis, Gerjan
- Numans, Mattijs E.
- Nyholt, Dale R.
- Penninx, Brenda W.
- Polidoro, Silvia
- Prokopenko, Inga
- Ricceri, Fulvio
- Santos, Eugenio
- Smit, Johannes H.
- Soranzo, Nicole
- Sovio, Ulla
- Thorgeirsson, Thorgeir E.
- Troakes, Claire
- Tönjes, Anke
- Uiterwaal, Cuno S.
- Vogelzangs, Nicole
- Wareham, Nicholas J.
- Waterworth, Dawn M.
- Whitfield, John B.
- Willemsen, Gonneke
- Yuan, Xin
- Zhai, Guangju
- Zhao, Jing H.
- Zhang, Weihua
- Martin, Nicholas G.
- Metspalu, Andres
- Scott, James
- Spector, Tim D.
- Loos, Ruth J.
- Boomsma, Dorret I.
- Mooser, Vincent
- Peltonen, Leena
- Vineis, Paolo
- Sommer, Wolfgang H.
- Kooner, Jaspal S.
- Spanagel, Rainer
- Elliott, Paul
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-04-06
- Volume
- 108
- Issue
- 17
- Pages
- 7119-7124
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3084048
- OpenAlex
- W2002212507
- Cited by
- 264
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 8 · 2022: 16 · 2021: 12 · 2020: 13 · 2019: 25 · 2018: 14 · 2017: 23 · 2016: 22 · 2015: 28 · 2014: 30 · 2013: 33 · 2012: 24
- FWCI
- 18.89
- Type
- journal article
- Language
- en
- Update notices
- correction (2011-05-13)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
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- PubMed Central (publishedVersion)
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- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Faculty of Health; Institute of Health and Biomedical Innovation
- WOS
- Funders
- Wellcome Trust (090532)
- National Institute for Health and Care Research (RD06/0020, 01GS08152)
- Research Councils UK
- Imperial College London
- Imperial College Healthcare NHS Trust
- European Commission (242257, RD06/0020, 201413, LSHMCT-2007-037286)
- Forskningsrådet för Arbetsliv och Socialvetenskap
- Junta de Castilla y León
- University of California, San Francisco (RD06/0020)
- Medical Research Council (LSHM-CT-2007-037286, RD06/0020, 01GS08152, 93558)
- Instituto de Salud Carlos III (RD06/0020)
- National Institute on Alcohol Abuse and Alcoholism (K02AA018755, K05AA017688)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- AUTS2, alcohol consumption, alcohol sensitivity, alcohol drinking behavior, prefrontal cortex gene expression, genetic susceptibility to alcoholism
- MeSH terms
- Alcohol Drinking, Animals, Cytoskeletal Proteins, Drosophila melanogaster, Female, Gene Expression Regulation, Genotype, Humans, Male, Nuclear Proteins, Proteins, Transcription Factors, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, White People, Mice, Genome-Wide Association Study
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