Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21471458
TITLE
Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.
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 × 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.
DATE PUBLISHED
2011 Apr 26
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/04/06
entrez 2011/04/08 06:00
pubmed 2011/04/08 06:00
medline 2011/06/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Schumann G Schumann Gunter G Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London SE5 8AF, United Kingdom. gunter.schumann@kcl.ac.uk
Coin LJ Coin Lachlan J LJ
Lourdusamy A Lourdusamy Anbarasu A
Charoen P Charoen Pimphen P
Berger KH Berger Karen H KH
Stacey D Stacey David D
Desrivières S Desrivières Sylvane S
Aliev FA Aliev Fazil A FA
Khan AA Khan Anokhi A AA
Amin N Amin Najaf N
Aulchenko YS Aulchenko Yurii S YS
Bakalkin G Bakalkin Georgy G
Bakker SJ Bakker Stephan J SJ
Balkau B Balkau Beverley B
Beulens JW Beulens Joline W JW
Bilbao A Bilbao Ainhoa A
de Boer RA de Boer Rudolf A RA
Beury D Beury Delphine D
Bots ML Bots Michiel L ML
Breetvelt EJ Breetvelt Elemi J EJ
Cauchi S Cauchi Stéphane S
Cavalcanti-Proença C Cavalcanti-Proença Christine C
Chambers JC Chambers John C JC
Clarke TK Clarke Toni-Kim TK
Dahmen N Dahmen Norbert N
de Geus EJ de Geus Eco J EJ
Dick D Dick Danielle D
Ducci F Ducci Francesca F
Easton A Easton Alanna A
Edenberg HJ Edenberg Howard J HJ
Esko T Esko Tõnu T
Esk T Esk Tõnu T
Fernández-Medarde A Fernández-Medarde Alberto A
Foroud T Foroud Tatiana T
Freimer NB Freimer Nelson B NB
Girault JA Girault Jean-Antoine JA
Grobbee DE Grobbee Diederick E DE
Guarrera S Guarrera Simonetta S
Gudbjartsson DF Gudbjartsson Daniel F DF
Hartikainen AL Hartikainen Anna-Liisa AL
Heath AC Heath Andrew C AC
Hesselbrock V Hesselbrock Victor V
Hofman A Hofman Albert A
Hottenga JJ Hottenga Jouke-Jan JJ
Isohanni MK Isohanni Matti K MK
Kaprio J Kaprio Jaakko J
Khaw KT Khaw Kay-Tee KT
Kuehnel B Kuehnel Brigitte B
Laitinen J Laitinen Jaana J
Lobbens S Lobbens Stéphane S
Luan J Luan Jian'an J
Mangino M Mangino Massimo M
Maroteaux M Maroteaux Matthieu M
Matullo G Matullo Giuseppe G
McCarthy MI McCarthy Mark I MI
Mueller C Mueller Christian C
Navis G Navis Gerjan G
Numans ME Numans Mattijs E ME
Núñez A Núñez Alejandro A
Nyholt DR Nyholt Dale R DR
Onland-Moret CN Onland-Moret Charlotte N CN
Oostra BA Oostra Ben A BA
O'Reilly PF O'Reilly Paul F PF
Palkovits M Palkovits Miklos M
Penninx BW Penninx Brenda W BW
Polidoro S Polidoro Silvia S
Pouta A Pouta Anneli A
Prokopenko I Prokopenko Inga I
Ricceri F Ricceri Fulvio F
Santos E Santos Eugenio E
Smit JH Smit Johannes H JH
Soranzo N Soranzo Nicole N
Song K Song Kijoung K
Sovio U Sovio Ulla U
Stumvoll M Stumvoll Michael M
Surakk I Surakk Ida I
Thorgeirsson TE Thorgeirsson Thorgeir E TE
Thorsteinsdottir U Thorsteinsdottir Unnur U
Troakes C Troakes Claire C
Tyrfingsson T Tyrfingsson Thorarinn T
Tönjes A Tönjes Anke A
Uiterwaal CS Uiterwaal Cuno S CS
Uitterlinden AG Uitterlinden Andre G AG
van der Harst P van der Harst Pim P
van der Schouw YT van der Schouw Yvonne T YT
Staehlin O Staehlin Oliver O
Vogelzangs N Vogelzangs Nicole N
Vollenweider P Vollenweider Peter P
Waeber G Waeber Gerard G
Wareham NJ Wareham Nicholas J NJ
Waterworth DM Waterworth Dawn M DM
Whitfield JB Whitfield John B JB
Wichmann EH Wichmann Erich H EH
Willemsen G Willemsen Gonneke G
Witteman JC Witteman Jacqueline C JC
Yuan X Yuan Xin X
Zhai G Zhai Guangju G
Zhao JH Zhao Jing H JH
Zhang W Zhang Weihua W
Martin NG Martin Nicholas G NG
Metspalu A Metspalu Andres A
Doering A Doering Angela A
Scott J Scott James J
Spector TD Spector Tim D TD
Loos RJ Loos Ruth J RJ
Boomsma DI Boomsma Dorret I DI
Mooser V Mooser Vincent V
Peltonen L Peltonen Leena L
Stefansson K Stefansson Kari K
van Duijn CM van Duijn Cornelia M CM
Vineis P Vineis Paolo P
Sommer WH Sommer Wolfgang H WH
Kooner JS Kooner Jaspal S JS
Spanagel R Spanagel Rainer R
Heberlein UA Heberlein Ulrike A UA
Jarvelin MR Jarvelin Marjo-Riitta MR
Elliott P Elliott Paul P
INVESTIGATORS
JOURNAL
VOLUME: 108
ISSUE: 17
TITLE: Proceedings of the National Academy of Sciences of the United States of America
ISOABBREVIATION: Proc. Natl. Acad. Sci. U.S.A.
YEAR: 2011
MONTH: Apr
DAY: 26
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1091-6490
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Proc Natl Acad Sci U S A
COUNTRY: United States
ISSNLINKING: 0027-8424
NLMUNIQUEID: 7505876
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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ErratumIn Proc Natl Acad Sci U S A. 2011 May 31;108(22):9316 20727682 Esk, Tõnu [corrected to Esko, Tõnu]
GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
G0401527 Medical Research Council United Kingdom
G0600676 Medical Research Council United Kingdom
G0601966 Medical Research Council United Kingdom
G0700931 Medical Research Council United Kingdom
G0701863 Medical Research Council United Kingdom
G0801056 Medical Research Council United Kingdom
G0901858 Medical Research Council United Kingdom
G1000143 Medical Research Council United Kingdom
K02 AA018755 NIAAA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MC_U106179471 Medical Research Council United Kingdom
MC_U106188470 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Alcohol Drinking metabolism
Animals metabolism
Drosophila melanogaster metabolism
European Continental Ancestry Group genetics
Female genetics
Gene Expression Regulation genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Male genetics
Mice genetics
Nuclear Proteins genetics
Polymorphism, Single Nucleotide genetics
Proteins metabolism
Quantitative Trait, Heritable metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 AUTS2 protein, human
0 Auts2 protein, mouse
0 Nuclear Proteins
0 Proteins
OTHER ID's
OTHERID SOURCE
PMC3084048 NLM