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 Esk; 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&apos;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&apos;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; Angela Doering; James Scott; Tim D. Spector; Ruth J. Loos; Dorret I. Boomsma; Vincent Mooser; Leena Peltonen; Kari Stefansson; Cornelia M. van Duijn; Paolo Vineis; Wolfgang H. Sommer; Jaspal S. Kooner; Rainer Spanagel; Ulrike A. Heberlein; Marjo-Riitta Jarvelin; Paul Elliott

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

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. BreetveltStephane 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 Esk, 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, Angela Doering, James Scott, Tim D. Spector, Ruth J. Loos, Dorret I. Boomsma, Vincent Mooser, Leena Peltonen, Kari Stefansson, Cornelia M. van Duijn, Paolo Vineis, Wolfgang H. Sommer, Jaspal S. Kooner, Rainer Spanagel, Ulrike A. Heberlein, Marjo-Riitta Jarvelin, Paul Elliott

Research output: Contribution to journal › Article › peer-review

231 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	7119 - 7124
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	108
Issue number	17
DOIs	https://doi.org/10.1073/pnas.1017288108
Publication status	Published - 26 Apr 2011

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10.1073/pnas.1017288108

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Schumann, G., Coin, L. J., Lourdusamy, A., Charoen, P., Berger, K. H., Stacey, D., Desrivieres, 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., ... Elliott, P. (2011). Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7119 - 7124. https://doi.org/10.1073/pnas.1017288108

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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",

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 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.",

author = "Gunter Schumann and Coin, {Lachlan J.} and Anbarasu Lourdusamy and Pimphen Charoen and Berger, {Karen H.} and David Stacey and Sylvane Desrivieres and Aliev, {Fazil A.} and Khan, {Anokhi A.} and Najaf Amin and Aulchenko, {Yurii S.} and Georgy Bakalkin and Bakker, {Stephan J.} and Beverley Balkau and Beulens, {Joline W.} and Ainhoa Bilbao and {de Boer}, {Rudolf A.} and Delphine Beury and Bots, {Michiel L.} and Breetvelt, {Elemi J.} and Stephane Cauchi and Christine Cavalcanti-Proenca and Chambers, {John C.} and Toni-Kim Clarke and Norbert Dahmen and {de Geus}, {Eco J.} and Danielle Dick and Francesca Ducci and Alanna Easton and Edenberg, {Howard J.} and Tonu Esk and Alberto Fernandez-Medarde and Tatiana Foroud and Freimer, {Nelson B.} and Jean-Antoine Girault and Grobbee, {Diederick E.} and Simonetta Guarrera and Gudbjartsson, {Daniel F.} and Anna-Liisa Hartikainen and Heath, {Andrew C.} and Victor Hesselbrock and Albert Hofman and Jouke-Jan Hottenga and Isohanni, {Matti K.} and Jaakko Kaprio and Kay-Tee Khaw and Brigitte Kuehnel and Jaana Laitinen and Stephane Lobbens and Jian'an Luan and Massimo Mangino and Matthieu Maroteaux and Giuseppe Matullo and McCarthy, {Mark I.} and Christian Mueller and Gerjan Navis and Numans, {Mattijs E.} and Alejandro Nunez and Nyholt, {Dale R.} and Onland-Moret, {Charlotte N.} and Oostra, {Ben A.} and O'Reilly, {Paul F.} and Miklos Palkovits and Penninx, {Brenda W.} and Silvia Polidoro and Anneli Pouta and Inga Prokopenko and Fulvio Ricceri and Eugenio Santos and Smit, {Johannes H.} and Nicole Soranzo and Kijoung Song and Ulla Sovio and Michael Stumvoll and Ida Surakk and Thorgeirsson, {Thorgeir E.} and Unnur Thorsteinsdottir and Claire Troakes and Thorarinn Tyrfingsson and Anke Toenjes and Uiterwaal, {Cuno S.} and Uitterlinden, {Andre G.} and {van der Harst}, Pim and {van der Schouw}, {Yvonne T.} and Oliver Staehlin and Nicole Vogelzangs and Peter Vollenweider and Gerard Waeber and Wareham, {Nicholas J.} and Waterworth, {Dawn M.} and Whitfield, {John B.} and Wichmann, {Erich H.} and Gonneke Willemsen and Witteman, {Jacqueline C.} and Xin Yuan and Guangju Zhai and Zhao, {Jing H.} and Weihua Zhang and Martin, {Nicholas G.} and Andres Metspalu and Angela Doering and James Scott and Spector, {Tim D.} and Loos, {Ruth J.} and Boomsma, {Dorret I.} and Vincent Mooser and Leena Peltonen and Kari Stefansson and {van Duijn}, {Cornelia M.} and Paolo Vineis and Sommer, {Wolfgang H.} and Kooner, {Jaspal S.} and Rainer Spanagel and Heberlein, {Ulrike A.} and Marjo-Riitta Jarvelin and Paul Elliott",

year = "2011",

month = apr,

day = "26",

doi = "10.1073/pnas.1017288108",

language = "English",

volume = "108",

pages = "7119 -- 7124",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "1091-6490",

publisher = "National Acad Sciences",

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Schumann, G, Coin, LJ, Lourdusamy, A, Charoen, P, Berger, KH, Stacey, D, Desrivieres, S, Aliev, FA, Khan, AA, Amin, N, Aulchenko, YS, Bakalkin, G, Bakker, SJ, Balkau, B, Beulens, JW, Bilbao, A, de Boer, RA, Beury, D, Bots, ML, Breetvelt, EJ, Cauchi, S, Cavalcanti-Proenca, C, Chambers, JC, Clarke, T-K, Dahmen, N, de Geus, EJ, Dick, D, Ducci, F , Easton, A, Edenberg, HJ, Esk, T, Fernandez-Medarde, A, Foroud, T, Freimer, NB, Girault, J-A, Grobbee, DE, Guarrera, S, Gudbjartsson, DF, Hartikainen, A-L, Heath, AC, Hesselbrock, V, Hofman, A, Hottenga, J-J, Isohanni, MK, Kaprio, J, Khaw, K-T, Kuehnel, B, Laitinen, J, Lobbens, S, Luan, J, Mangino, M, Maroteaux, M, Matullo, G, McCarthy, MI, Mueller, C, Navis, G, Numans, ME, Nunez, A, Nyholt, DR, Onland-Moret, CN, Oostra, BA, O'Reilly, PF, Palkovits, M, Penninx, BW, Polidoro, S, Pouta, A, Prokopenko, I, Ricceri, F, Santos, E, Smit, JH, Soranzo, N, Song, K, Sovio, U, Stumvoll, M, Surakk, I, Thorgeirsson, TE, Thorsteinsdottir, U, Troakes, C, Tyrfingsson, T, Toenjes, A, Uiterwaal, CS, Uitterlinden, AG, van der Harst, P, van der Schouw, YT, Staehlin, O, Vogelzangs, N, Vollenweider, P, Waeber, G, Wareham, NJ, Waterworth, DM, Whitfield, JB, Wichmann, EH, Willemsen, G, Witteman, JC, Yuan, X, Zhai, G, Zhao, JH, Zhang, W, Martin, NG, Metspalu, A, Doering, A, Scott, J, Spector, TD, Loos, RJ, Boomsma, DI, Mooser, V, Peltonen, L, Stefansson, K, van Duijn, CM, Vineis, P, Sommer, WH, Kooner, JS, Spanagel, R, Heberlein, UA, Jarvelin, M-R & Elliott, P 2011, 'Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 17, pp. 7119 - 7124. https://doi.org/10.1073/pnas.1017288108

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. / Schumann, Gunter; Coin, Lachlan J.; Lourdusamy, Anbarasu et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 17, 26.04.2011, p. 7119 - 7124.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

AU - Schumann, Gunter

AU - Coin, Lachlan J.

AU - Lourdusamy, Anbarasu

AU - Charoen, Pimphen

AU - Berger, Karen H.

AU - Stacey, David

AU - Desrivieres, Sylvane

AU - Aliev, Fazil A.

AU - Khan, Anokhi A.

AU - Amin, Najaf

AU - Aulchenko, Yurii S.

AU - Bakalkin, Georgy

AU - Bakker, Stephan J.

AU - Balkau, Beverley

AU - Beulens, Joline W.

AU - Bilbao, Ainhoa

AU - de Boer, Rudolf A.

AU - Beury, Delphine

AU - Bots, Michiel L.

AU - Breetvelt, Elemi J.

AU - Cauchi, Stephane

AU - Cavalcanti-Proenca, Christine

AU - Chambers, John C.

AU - Clarke, Toni-Kim

AU - Dahmen, Norbert

AU - de Geus, Eco J.

AU - Dick, Danielle

AU - Ducci, Francesca

AU - Easton, Alanna

AU - Edenberg, Howard J.

AU - Esk, Tonu

AU - Fernandez-Medarde, Alberto

AU - Foroud, Tatiana

AU - Freimer, Nelson B.

AU - Girault, Jean-Antoine

AU - Grobbee, Diederick E.

AU - Guarrera, Simonetta

AU - Gudbjartsson, Daniel F.

AU - Hartikainen, Anna-Liisa

AU - Heath, Andrew C.

AU - Hesselbrock, Victor

AU - Hofman, Albert

AU - Hottenga, Jouke-Jan

AU - Isohanni, Matti K.

AU - Kaprio, Jaakko

AU - Khaw, Kay-Tee

AU - Kuehnel, Brigitte

AU - Laitinen, Jaana

AU - Lobbens, Stephane

AU - Luan, Jian'an

AU - Mangino, Massimo

AU - Maroteaux, Matthieu

AU - Matullo, Giuseppe

AU - McCarthy, Mark I.

AU - Mueller, Christian

AU - Navis, Gerjan

AU - Numans, Mattijs E.

AU - Nunez, Alejandro

AU - Nyholt, Dale R.

AU - Onland-Moret, Charlotte N.

AU - Oostra, Ben A.

AU - O'Reilly, Paul F.

AU - Palkovits, Miklos

AU - Penninx, Brenda W.

AU - Polidoro, Silvia

AU - Pouta, Anneli

AU - Prokopenko, Inga

AU - Ricceri, Fulvio

AU - Santos, Eugenio

AU - Smit, Johannes H.

AU - Soranzo, Nicole

AU - Song, Kijoung

AU - Sovio, Ulla

AU - Stumvoll, Michael

AU - Surakk, Ida

AU - Thorgeirsson, Thorgeir E.

AU - Thorsteinsdottir, Unnur

AU - Troakes, Claire

AU - Tyrfingsson, Thorarinn

AU - Toenjes, Anke

AU - Uiterwaal, Cuno S.

AU - Uitterlinden, Andre G.

AU - van der Harst, Pim

AU - van der Schouw, Yvonne T.

AU - Staehlin, Oliver

AU - Vogelzangs, Nicole

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Wareham, Nicholas J.

AU - Waterworth, Dawn M.

AU - Whitfield, John B.

AU - Wichmann, Erich H.

AU - Willemsen, Gonneke

AU - Witteman, Jacqueline C.

AU - Yuan, Xin

AU - Zhai, Guangju

AU - Zhao, Jing H.

AU - Zhang, Weihua

AU - Martin, Nicholas G.

AU - Metspalu, Andres

AU - Doering, Angela

AU - Scott, James

AU - Spector, Tim D.

AU - Loos, Ruth J.

AU - Boomsma, Dorret I.

AU - Mooser, Vincent

AU - Peltonen, Leena

AU - Stefansson, Kari

AU - van Duijn, Cornelia M.

AU - Vineis, Paolo

AU - Sommer, Wolfgang H.

AU - Kooner, Jaspal S.

AU - Spanagel, Rainer

AU - Heberlein, Ulrike A.

AU - Jarvelin, Marjo-Riitta

AU - Elliott, Paul

PY - 2011/4/26

Y1 - 2011/4/26

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.1017288108

DO - 10.1073/pnas.1017288108

M3 - Article

SN - 1091-6490

VL - 108

SP - 7119

EP - 7124

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

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

IS - 17

ER -

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

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