Abstract
Original language | Undefined/Unknown |
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Pages (from-to) | 7119-7124 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of Ame |
Volume | 108 |
Issue number | 17 |
DOIs | |
Publication status | Published - 2011 |
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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; Charoen, P; Berger, KH; Stacey, D; Desrivieres, S; Aliev, FA; Khan, AA; Amin, Najaf; Aulchenko, YS; Bakalkin, G; Bakker, SJ; Balkau, B; Beulens, JW; Bilbao, A; de Boer, RA; Beury, D; Bots, ML (Michiel); 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 (Diederick); Guarrera, S; Gudbjartsson, DF; Hartikainen, AL; Heath, AC; Hesselbrock, V; Hofman, Bert; Hottenga, JJ (Jouke Jan); 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, Ben; 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, André; 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, Cornelia; Vineis, P; Sommer, WH; Kooner, JS; Spanagel, R; Heberlein, UA; Jarvelin, MR; Elliott, P.
In: Proceedings of the National Academy of Sciences of the United States of Ame, 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
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
SN - 0027-8424
IS - 17
ER -