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

Gunter Schumann; Lachlan J. Coin; Anbarasu Lourdusamy; Pimphen Charoen; Karen H. Berger; David Stacey; Sylvane Desrivieres; 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; Stephane Cauchi; Christine Cavalcanti-Proenca; John C. Chambers; Toni-Kim Clarke; Norbert Dahmen; Eco J. de Geus; Danielle Dick; Francesca Ducci; Alanna Easton; Howard J. Edenberg; Tonu Esko; Alberto Fernandez-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; Stephane Lobbens; Jian'an Luan; Massimo Mangino; Matthieu Maroteaux; Giuseppe Matullo; Mark I. McCarthy; Christian Mueller; Gerjan Navis; Mattijs E. Numans; Alejandro Nunez; 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 Toenjes; Cuno S. Uiterwaal; Andre G. Uitterlinden; Pim van der Harst; Yvonne T. van der Schouw; Oliver Staehlin; Nicole Vogelzangs; Peter Vollenweider; Gerard Waeber; Nicholas J. Wareham; Dawn M. Waterworth; John B. Whitfield; Erich H. Wichmann; Gonneke Willemsen; Jacqueline C. Witteman; Xin Yuan; Guangju Zhai; Jing H. Zhao; Weihua Zhang; Nicholas G. Martin; Andres Metspalu

doi:10.1073/pnas.1017288108

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

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

Gunter Schumann, Lachlan J. Coin, Anbarasu Lourdusamy, Pimphen Charoen, Karen H. Berger, David Stacey, Sylvane Desrivieres, Fazil A. Aliev, Anokhi A. Khan, Najaf Amin, …

Proceedings of the National Academy of Sciences - PNAS, Vol.108(17), pp.7119-7124

26/04/2011

DOI: https://doi.org/10.1073/pnas.1017288108

PMID: 21471458

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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 similar to 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.

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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
Creators: Gunter Schumann - King's College London
Lachlan J. Coin - Imperial College London
Anbarasu Lourdusamy - King's College London
Pimphen Charoen - Mahidol Oxford Tropical Medicine Research Unit
Karen H. Berger - Ernest Gallo Clinic and Research Center
David Stacey - King's College London
Sylvane Desrivieres - Medical Research Council
Fazil A. Aliev - Virginia Commonwealth University
Anokhi A. Khan - Imperial College London
Najaf Amin - College Station Medical Center
Yurii S. Aulchenko - College Station Medical Center
Georgy Bakalkin - Uppsala University
Stephan J. Bakker - University Medical Center Groningen
Beverley Balkau - Inserm
Joline W. Beulens - University Medical Center Utrecht
Ainhoa Bilbao - Central Institute of Mental Health
Rudolf A. de Boer - University Medical Center Groningen
Delphine Beury - Institut de Biologie de Lille
Michiel L. Bots - University Medical Center Utrecht
Elemi J. Breetvelt - University Medical Center Utrecht
Stephane Cauchi - Institut de Biologie de Lille
Christine Cavalcanti-Proenca - Institut de Biologie de Lille
John C. Chambers - Imperial College London
Toni-Kim Clarke - College Station Medical Center
Norbert Dahmen - Johannes Gutenberg University Mainz
Eco J. de Geus - Indiana University – Purdue University Indianapolis
Danielle Dick - Virginia Commonwealth University
Francesca Ducci - King's College London
Alanna Easton - King's College London
Howard J. Edenberg - Indiana University – Purdue University Indianapolis
Tonu Esko - Estonian Biocentre
Alberto Fernandez-Medarde - Centro de Investigación del Cáncer
Tatiana Foroud - Indiana University – Purdue University Indianapolis
Nelson B. Freimer - University of California, Los Angeles
Jean-Antoine Girault - Univ Paris 06, INSERM, Inst Fer Moulin, F-75005 Paris, France
Diederick E. Grobbee - Central Institute of Mental Health
Simonetta Guarrera - Institute for Scientific Interchange
Daniel F. Gudbjartsson - University of Iceland
Anna-Liisa Hartikainen - University of Oulu
Andrew C. Heath - Washington University in St. Louis
Victor Hesselbrock - University of Connecticut
Albert Hofman - College Station Medical Center
Jouke-Jan Hottenga - University of Amsterdam
Matti K. Isohanni - University of Oulu
Jaakko Kaprio - University of Helsinki
Kay-Tee Khaw - University of Cambridge
Brigitte Kuehnel - Helmholtz Zentrum München
Jaana Laitinen - Finnish Institute of Occupational Health
Stephane Lobbens - Institut de Biologie de Lille
Jian'an Luan - College Station Medical Center
Massimo Mangino - King's College London
Matthieu Maroteaux - Sorbonne Université
Giuseppe Matullo - University of Turin
Mark I. McCarthy - Oxford Centre for Diabetes, Endocrinology and Metabolism
Christian Mueller - King's College London
Gerjan Navis - University Medical Center Groningen
Mattijs E. Numans - University Medical Center Utrecht
Alejandro Nunez - Centro de Investigación del Cáncer
Dale R. Nyholt - QIMR Berghofer Medical Research Institute
Charlotte N. Onland-Moret - University Medical Center Utrecht
Ben A. Oostra - Uppsala University
Paul F. O'Reilly
Miklos Palkovits - Semmelweis University
Brenda W. Penninx - University of Amsterdam
Silvia Polidoro - Institute for Scientific Interchange
Anneli Pouta - Finnish Institute for Health and Welfare
Inga Prokopenko - Wellcome Centre for Human Genetics
Fulvio Ricceri - Institute for Scientific Interchange
Eugenio Santos - Consejo Superior de Investigaciones Científicas
Johannes H. Smit - EMGO Institute for Health and Care Research
Nicole Soranzo - Wellcome Sanger Institute
Kijoung Song - GlaxoSmithKline
Ulla Sovio - Imperial College London
Michael Stumvoll - Leipzig University
Ida Surakk - Institute for Molecular Medicine Finland
Thorgeir E. Thorgeirsson - University of Iceland
Unnur Thorsteinsdottir - University of Iceland
Claire Troakes - King's College London
Thorarinn Tyrfingsson - Vogur Samtok Ahugafolks Afengis Addict Treatment, IS-112 Reykjavik, Iceland
Anke Toenjes - College Station Medical Center
Cuno S. Uiterwaal - University of Groningen
Andre G. Uitterlinden - Erasmus MC
Pim van der Harst - University Medical Center Groningen
Yvonne T. van der Schouw - University Medical Center Utrecht
Oliver Staehlin - Central Institute of Mental Health
Nicole Vogelzangs - EMGO Institute for Health and Care Research
Peter Vollenweider - University Hospital of Lausanne
Gerard Waeber - University Hospital of Lausanne
Nicholas J. Wareham - MRC Epidemiology Unit
Dawn M. Waterworth - GlaxoSmithKline
John B. Whitfield - QIMR Berghofer Medical Research Institute
Erich H. Wichmann - Helmholtz Zentrum München
Gonneke Willemsen - Vrije Universiteit Amsterdam
Jacqueline C. Witteman - Erasmus MC
Xin Yuan - GlaxoSmithKline
Guangju Zhai - King's College London
Jing H. Zhao - College Station Medical Center
Weihua Zhang - Imperial College London
Nicholas G. Martin - QIMR Berghofer Medical Research Institute
Andres Metspalu - University of Tartu
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.108(17), pp.7119-7124
Publisher: Natl Acad Sciences
Number of pages: 6
Date published: 26/04/2011
Grant note: G0601966; G0600676; G0901858; G0701863; G0700931; G0801056; MC_U106188470 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Swedish Science Research Council FIS PI021570 / Instituto de Salud Carlos III (ISCIII); Instituto de Salud Carlos III; Spanish Government Research Council United Kingdom (RCUK); UK Research & Innovation (UKRI) G0600676; G0801056; G0700931; G1000143; MC_U106179471; MC_U106188470; G0901858; G0401527; G9817803B; G0701863; G0601966; G0801056B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NIHR; National Institutes of Health Research (NIHR) 93558 / United Kingdom National Institute for Health Research (NIHR) Biomedical Research Centre Mental Health, the Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); National Institutes of Health Research (NIHR) SA044A08; GR93 / Junta de Castilla y Leon (JCyL); Junta de Castilla y Leon 01GS08152 / German Nationales Genomforschungsnetz RD06/0020/000 / RTICC, ISCIII, Spain; Instituto de Salud Carlos III
Identifiers: 99928703502346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

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

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