Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826261391599730688 |
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| author | Schumann, G Coin, L Lourdusamy, A Charoen, P Berger, K Stacey, D Desrivières, S Aliev, F Khan, A Amin, N Aulchenko, Y Bakalkin, G Bakker, S Balkau, B Beulens, J Bilbao, A de Boer, R Beury, D Bots, M Breetvelt, E Cauchi, S Cavalcanti-Proença, C Chambers, J Clarke, T Dahmen, N |
| author_facet | Schumann, G Coin, L Lourdusamy, A Charoen, P Berger, K Stacey, D Desrivières, S Aliev, F Khan, A Amin, N Aulchenko, Y Bakalkin, G Bakker, S Balkau, B Beulens, J Bilbao, A de Boer, R Beury, D Bots, M Breetvelt, E Cauchi, S Cavalcanti-Proença, C Chambers, J Clarke, T Dahmen, N |
| author_sort | Schumann, G |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:20:41Z |
| format | Journal article |
| id | oxford-uuid:19fc4e7d-70a0-4c93-90d2-ad6b4202e918 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:20:41Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:19fc4e7d-70a0-4c93-90d2-ad6b4202e9182022-03-26T10:52:10ZGenome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:19fc4e7d-70a0-4c93-90d2-ad6b4202e918EnglishSymplectic Elements at Oxford2011Schumann, GCoin, LLourdusamy, ACharoen, PBerger, KStacey, DDesrivières, SAliev, FKhan, AAmin, NAulchenko, YBakalkin, GBakker, SBalkau, BBeulens, JBilbao, Ade Boer, RBeury, DBots, MBreetvelt, ECauchi, SCavalcanti-Proença, CChambers, JClarke, TDahmen, NAlcohol 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. |
| spellingShingle | Schumann, G Coin, L Lourdusamy, A Charoen, P Berger, K Stacey, D Desrivières, S Aliev, F Khan, A Amin, N Aulchenko, Y Bakalkin, G Bakker, S Balkau, B Beulens, J Bilbao, A de Boer, R Beury, D Bots, M Breetvelt, E Cauchi, S Cavalcanti-Proença, C Chambers, J Clarke, T Dahmen, N Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. |
| title | Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. |
| title_full | Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. |
| title_fullStr | Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. |
| title_full_unstemmed | Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. |
| title_short | Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. |
| title_sort | genome wide association and genetic functional studies identify autism susceptibility candidate 2 gene auts2 in the regulation of alcohol consumption |
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