Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

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.; Esk, 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.

doi:10.1073/pnas.1017288108

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Détails

Télécharger: BIB_1A1C34CA4648.P001.pdf (352.26 [Ko])
Etat: Public
Version: de l'auteur⸱e

ID Serval

serval:BIB_1A1C34CA4648

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Périodique

Proceedings of the National Academy of Sciences of the United States of America

Auteur⸱e⸱s

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., Esk 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.

ISSN

1091-6490 (Electronic)

ISSN-L

0027-8424

Statut éditorial

Publié

Date de publication

2011

Peer-reviewed

Oui

Volume

108

Numéro

Pages

7119-7124

Langue

anglais

Notes

Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Résumé

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.

Mots-clé

Alcohol Drinking/genetics, Alcohol Drinking/metabolism, Animals, Drosophila melanogaster/genetics, Drosophila melanogaster/metabolism, European Continental Ancestry Group/genetics, Female, Gene Expression Regulation/genetics, Genome-Wide Association Study, Genotype, Humans, Male, Mice, Nuclear Proteins/biosynthesis, Nuclear Proteins/genetics, Polymorphism, Single Nucleotide, Proteins/genetics, Proteins/metabolism, Quantitative Trait, Heritable

URN

urn:nbn:ch:serval-BIB_1A1C34CA46481

OAI-PMH

oai:serval.unil.ch:BIB_1A1C34CA4648

DOI

10.1073/pnas.1017288108

Pubmed

21471458

Web of science

000289888500082

Open Access

Oui