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

G Schumann; LJ Coin; A Lourdusamy; P Charoen; KH Berger; D Stacey; S Desrivieres; FA Aliev; AA Khan; Najaf Amin; YS Aulchenko; G Bakalkin; SJ Bakker; B Balkau; JW Beulens; A Bilbao; RA de Boer; D Beury; ML (Michiel) Bots; EJ Breetvelt; S Cauchi; C Cavalcanti-Proenca; JC Chambers; TK Clarke; N Dahmen; EJ de Geus; D Dick; F Ducci; A Easton; HJ Edenberg; T Esk; A Fernandez-Medarde; T Foroud; NB Freimer; JA Girault; DE (Diederick) Grobbee; S Guarrera; DF Gudbjartsson; AL Hartikainen; AC Heath; V Hesselbrock; Bert Hofman; JJ (Jouke Jan) Hottenga; MK Isohanni; J Kaprio; KT Khaw; B Kuehnel; J Laitinen; S Lobbens; JA Luan; M Mangino; M Maroteaux; G Matullo; MI McCarthy; C Mueller; G Navis; ME Numans; A Nunez; DR Nyholt; CN Onland-Moret; Ben Oostra; PF O'Reilly; M Palkovits; BW Penninx; S Polidoro; A Pouta; I Prokopenko; F Ricceri; E Santos; JH Smit; N Soranzo; K Song; U Sovio; M Stumvoll; I Surakk; TE Thorgeirsson; U Thorsteinsdottir; C Troakes; T Tyrfingsson; A Tonjes; CS Uiterwaal; André Uitterlinden; P van der Harst; YT van der Schouw; O Staehlin; N Vogelzangs; P Vollenweider; G Waeber; NJ Wareham; DM Waterworth; JB Whitfield; EH Wichmann; G Willemsen; JCM Witteman; X Yuan; GJ Zhai; JH Zhao; WH Zhang; NG Martin; A Metspalu; A Doering; J Scott; TD Spector; RJ Loos; DI Boomsma; V Mooser; L Peltonen; K Stefansson; Cornelia Duijn; P Vineis; WH Sommer; JS Kooner; R Spanagel; UA Heberlein; MR Jarvelin; P 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

G Schumann, LJ Coin, A Lourdusamy, P Charoen, KH Berger, D Stacey, S Desrivieres, FA Aliev, AA Khan, Najaf Amin, YS Aulchenko, G Bakalkin, SJ Bakker, B Balkau, JW Beulens, A Bilbao, RA de Boer, D Beury, ML (Michiel) Bots, EJ BreetveltS Cauchi, C Cavalcanti-Proenca, JC Chambers, TK Clarke, N Dahmen, EJ de Geus, D Dick, F Ducci, A Easton, HJ Edenberg, T Esk, A Fernandez-Medarde, T Foroud, NB Freimer, JA Girault, DE (Diederick) Grobbee, S Guarrera, DF Gudbjartsson, AL Hartikainen, AC Heath, V Hesselbrock, Bert Hofman, JJ (Jouke Jan) Hottenga, MK Isohanni, J Kaprio, KT Khaw, B Kuehnel, J Laitinen, S Lobbens, JA Luan, M Mangino, M Maroteaux, G Matullo, MI McCarthy, C Mueller, G Navis, ME Numans, A Nunez, DR Nyholt, CN Onland-Moret, Ben Oostra, PF O'Reilly, M Palkovits, BW Penninx, S Polidoro, A Pouta, I Prokopenko, F Ricceri, E Santos, JH Smit, N Soranzo, K Song, U Sovio, M Stumvoll, I Surakk, TE Thorgeirsson, U Thorsteinsdottir, C Troakes, T Tyrfingsson, A Tonjes, CS Uiterwaal, André Uitterlinden, P van der Harst, YT van der Schouw, O Staehlin, N Vogelzangs, P Vollenweider, G Waeber, NJ Wareham, DM Waterworth, JB Whitfield, EH Wichmann, G Willemsen, JCM Witteman, X Yuan, GJ Zhai, JH Zhao, WH Zhang, NG Martin, A Metspalu, A Doering, J Scott, TD Spector, RJ Loos, DI Boomsma, V Mooser, L Peltonen, K Stefansson, Cornelia Duijn, P Vineis, WH Sommer, JS Kooner, R Spanagel, UA Heberlein, MR Jarvelin, P Elliott

Research output: Contribution to journal › Article › Academic › 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	Undefined/Unknown
Pages (from-to)	7119-7124
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the U.S.A.
Volume	108
Issue number	17
DOIs	https://doi.org/10.1073/pnas.1017288108
Publication status	Published - 2011

Research programs

EMC MGC-02-96-01
EMC MM-01-25-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02

Access to Document

10.1073/pnas.1017288108

http://hdl.handle.net/1765/33466

Cite this

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., ... 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 U.S.A., 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 = "G Schumann and LJ Coin and A Lourdusamy and P Charoen and KH Berger and D Stacey and S Desrivieres and FA Aliev and AA Khan and Najaf Amin and YS Aulchenko and G Bakalkin and SJ Bakker and B Balkau and JW Beulens and A Bilbao and {de Boer}, RA and D Beury and Bots, {ML (Michiel)} and EJ Breetvelt and S Cauchi and C Cavalcanti-Proenca and JC Chambers and TK Clarke and N Dahmen and {de Geus}, EJ and D Dick and F Ducci and A Easton and HJ Edenberg and T Esk and A Fernandez-Medarde and T Foroud and NB Freimer and JA Girault and Grobbee, {DE (Diederick)} and S Guarrera and DF Gudbjartsson and AL Hartikainen and AC Heath and V Hesselbrock and Bert Hofman and Hottenga, {JJ (Jouke Jan)} and MK Isohanni and J Kaprio and KT Khaw and B Kuehnel and J Laitinen and S Lobbens and JA Luan and M Mangino and M Maroteaux and G Matullo and MI McCarthy and C Mueller and G Navis and ME Numans and A Nunez and DR Nyholt and CN Onland-Moret and Ben Oostra and PF O'Reilly and M Palkovits and BW Penninx and S Polidoro and A Pouta and I Prokopenko and F Ricceri and E Santos and JH Smit and N Soranzo and K Song and U Sovio and M Stumvoll and I Surakk and TE Thorgeirsson and U Thorsteinsdottir and C Troakes and T Tyrfingsson and A Tonjes and CS Uiterwaal and Andr{\'e} Uitterlinden and {van der Harst}, P and {van der Schouw}, YT and O Staehlin and N Vogelzangs and P Vollenweider and G Waeber and NJ Wareham and DM Waterworth and JB Whitfield and EH Wichmann and G Willemsen and JCM Witteman and X Yuan and GJ Zhai and JH Zhao and WH Zhang and NG Martin and A Metspalu and A Doering and J Scott and TD Spector and RJ Loos and DI Boomsma and V Mooser and L Peltonen and K Stefansson and Cornelia Duijn and P Vineis and WH Sommer and JS Kooner and R Spanagel and UA Heberlein and MR Jarvelin and P Elliott",

year = "2011",

doi = "10.1073/pnas.1017288108",

language = "Undefined/Unknown",

volume = "108",

pages = "7119--7124",

journal = "Proceedings of the National Academy of Sciences of the U.S.A.",

issn = "0027-8424",

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number = "17",

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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, TK, Dahmen, N, de Geus, EJ, Dick, D, Ducci, F, Easton, A, Edenberg, HJ, Esk, T, Fernandez-Medarde, A, Foroud, T, Freimer, NB, Girault, JA, Grobbee, DE, Guarrera, S, Gudbjartsson, DF, Hartikainen, AL, Heath, AC, Hesselbrock, V, Hofman, B, Hottenga, JJ, Isohanni, MK, Kaprio, J, Khaw, KT, Kuehnel, B, Laitinen, J, Lobbens, S, Luan, JA, Mangino, M, Maroteaux, M, Matullo, G, McCarthy, MI, Mueller, C, Navis, G, Numans, ME, Nunez, A, Nyholt, DR, Onland-Moret, CN, Oostra, B, 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, Tonjes, A, Uiterwaal, CS, Uitterlinden, A, 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, JCM, Yuan, X, Zhai, GJ, Zhao, JH, Zhang, WH, Martin, NG, Metspalu, A, Doering, A, Scott, J, Spector, TD, Loos, RJ, Boomsma, DI, Mooser, V, Peltonen, L, Stefansson, K, Duijn, C, Vineis, P, Sommer, WH, Kooner, JS, Spanagel, R, Heberlein, UA, Jarvelin, MR & 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 U.S.A., 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, G; Coin, LJ; Lourdusamy, A et al.
In: Proceedings of the National Academy of Sciences of the U.S.A., Vol. 108, No. 17, 2011, p. 7119-7124.

Research output: Contribution to journal › Article › Academic › 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, G

AU - Coin, LJ

AU - Lourdusamy, A

AU - Charoen, P

AU - Berger, KH

AU - Stacey, D

AU - Desrivieres, S

AU - Aliev, FA

AU - Khan, AA

AU - Amin, Najaf

AU - Aulchenko, YS

AU - Bakalkin, G

AU - Bakker, SJ

AU - Balkau, B

AU - Beulens, JW

AU - Bilbao, A

AU - de Boer, RA

AU - Beury, D

AU - Bots, ML (Michiel)

AU - Breetvelt, EJ

AU - Cauchi, S

AU - Cavalcanti-Proenca, C

AU - Chambers, JC

AU - Clarke, TK

AU - Dahmen, N

AU - de Geus, EJ

AU - Dick, D

AU - Ducci, F

AU - Easton, A

AU - Edenberg, HJ

AU - Esk, T

AU - Fernandez-Medarde, A

AU - Foroud, T

AU - Freimer, NB

AU - Girault, JA

AU - Grobbee, DE (Diederick)

AU - Guarrera, S

AU - Gudbjartsson, DF

AU - Hartikainen, AL

AU - Heath, AC

AU - Hesselbrock, V

AU - Hofman, Bert

AU - Hottenga, JJ (Jouke Jan)

AU - Isohanni, MK

AU - Kaprio, J

AU - Khaw, KT

AU - Kuehnel, B

AU - Laitinen, J

AU - Lobbens, S

AU - Luan, JA

AU - Mangino, M

AU - Maroteaux, M

AU - Matullo, G

AU - McCarthy, MI

AU - Mueller, C

AU - Navis, G

AU - Numans, ME

AU - Nunez, A

AU - Nyholt, DR

AU - Onland-Moret, CN

AU - Oostra, Ben

AU - O'Reilly, PF

AU - Palkovits, M

AU - Penninx, BW

AU - Polidoro, S

AU - Pouta, A

AU - Prokopenko, I

AU - Ricceri, F

AU - Santos, E

AU - Smit, JH

AU - Soranzo, N

AU - Song, K

AU - Sovio, U

AU - Stumvoll, M

AU - Surakk, I

AU - Thorgeirsson, TE

AU - Thorsteinsdottir, U

AU - Troakes, C

AU - Tyrfingsson, T

AU - Tonjes, A

AU - Uiterwaal, CS

AU - Uitterlinden, André

AU - van der Harst, P

AU - van der Schouw, YT

AU - Staehlin, O

AU - Vogelzangs, N

AU - Vollenweider, P

AU - Waeber, G

AU - Wareham, NJ

AU - Waterworth, DM

AU - Whitfield, JB

AU - Wichmann, EH

AU - Willemsen, G

AU - Witteman, JCM

AU - Yuan, X

AU - Zhai, GJ

AU - Zhao, JH

AU - Zhang, WH

AU - Martin, NG

AU - Metspalu, A

AU - Doering, A

AU - Scott, J

AU - Spector, TD

AU - Loos, RJ

AU - Boomsma, DI

AU - Mooser, V

AU - Peltonen, L

AU - Stefansson, K

AU - Duijn, Cornelia

AU - Vineis, P

AU - Sommer, WH

AU - Kooner, JS

AU - Spanagel, R

AU - Heberlein, UA

AU - Jarvelin, MR

AU - Elliott, P

PY - 2011

Y1 - 2011

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

C2 - 21471458

SN - 0027-8424

VL - 108

SP - 7119

EP - 7124

JO - Proceedings of the National Academy of Sciences of the U.S.A.

JF - Proceedings of the National Academy of Sciences of the U.S.A.

IS - 17

ER -