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 Desrivières; Fazil A Aliev; Anokhi A Khan; Najaf Amin; Yurii S. Aulchenko; Georgy Bakalkin; Stephan JL Bakker; Beverley Balkau; Joline W Beulens; Ainhoa Bilbao; Rudolf A. de Boer; Delphine Beury; Michiel L Bots; Elemi J Breetvelt; Stéphane Cauchi; Christine Cavalcanti-Proença; John C. Chambers; Toni-Kim Clarke; Norbert Dahmen; Eco J. C. de Geus; Danielle M. DIck; Francesca Ducci; Alanna Easton; Howard J Edenberg; Tõnu Esko; Tõnu Esk; Alberto Fernández-Medarde; Tatiana M. 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; Stéphane Lobbens; Jian'an Luan; Massimo Mangino; Matthieu Maroteaux; Giuseppe Matullo; Mark I. McCarthy; Christian Mueller; Gerjan J. Navis; Mattijs E Numans; Alejandro Núñez; Dale R. Nyholt; Charlotte N Onland-Moret; Ben A. Oostra; Paul F. O'Reilly; Miklos Palkovits; Brenda Wjh 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 Tönjes; 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; H-Erich Wichmann; Gonneke Willemsen; Jacqueline C. Witteman; Xin Yuan; Guangju Zhai; Jing Hua Zhao; Weihua Zhang; Nicholas G. Martin; Andres Metspalu; Angela Doering; James Scott; Tim D. Spector; Ruth Jf 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 Desrivières, Fazil A Aliev, Anokhi A Khan, Najaf Amin, Yurii S. Aulchenko, Georgy Bakalkin, Stephan JL Bakker, Beverley Balkau, Joline W Beulens, Ainhoa Bilbao, Rudolf A. de Boer, Delphine Beury, Michiel L Bots, Elemi J BreetveltStéphane Cauchi, Christine Cavalcanti-Proença, John C. Chambers, Toni-Kim Clarke, Norbert Dahmen, Eco J. C. de Geus, Danielle M. DIck, Francesca Ducci, Alanna Easton, Howard J Edenberg, Tõnu Esko, Tõnu Esk, Alberto Fernández-Medarde, Tatiana M. 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, Stéphane Lobbens, Jian'an Luan, Massimo Mangino, Matthieu Maroteaux, Giuseppe Matullo, Mark I. McCarthy, Christian Mueller, Gerjan J. Navis, Mattijs E Numans, Alejandro Núñez, Dale R. Nyholt, Charlotte N Onland-Moret, Ben A. Oostra, Paul F. O'Reilly, Miklos Palkovits, Brenda Wjh 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 Tönjes, 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, H-Erich Wichmann, Gonneke Willemsen, Jacqueline C. Witteman, Xin Yuan, Guangju Zhai, Jing Hua Zhao, Weihua Zhang, Nicholas G. Martin, Andres Metspalu, Angela Doering, James Scott, Tim D. Spector, Ruth Jf 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 › Academic › peer-review

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.

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

Keywords

Alcohol Drinking
Animals
Drosophila melanogaster
European Continental Ancestry Group
Female
Gene Expression Regulation
Genome-Wide Association Study
Genotype
Humans
Male
Mice
Nuclear Proteins
Polymorphism, Single Nucleotide
Proteins
Quantitative Trait, Heritable
Journal Article
Research Support, Non-U.S. Gov't

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10.1073/pnas.1017288108

Cite this

Schumann, G., Coin, L. J., Lourdusamy, A., Charoen, P., Berger, K. H., Stacey, D., Desrivières, S., Aliev, F. A., Khan, A. A., Amin, N., Aulchenko, Y. S., Bakalkin, G., Bakker, S. JL., 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

@article{7423ae38f51c4ac2af159ce9412d66eb,

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.",

keywords = "Alcohol Drinking, Animals, Drosophila melanogaster, European Continental Ancestry Group, Female, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Male, Mice, Nuclear Proteins, Polymorphism, Single Nucleotide, Proteins, Quantitative Trait, Heritable, Journal Article, Research Support, Non-U.S. Gov't",

author = "Gunter Schumann and Coin, {Lachlan J} and Anbarasu Lourdusamy and Pimphen Charoen and Berger, {Karen H} and David Stacey and Sylvane Desrivi{\`e}res and Aliev, {Fazil A} and Khan, {Anokhi A} and Najaf Amin and Aulchenko, {Yurii S.} and Georgy Bakalkin and Bakker, {Stephan JL} 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 St{\'e}phane Cauchi and Christine Cavalcanti-Proen{\c c}a and Chambers, {John C.} and Toni-Kim Clarke and Norbert Dahmen and {de Geus}, {Eco J. C.} and DIck, {Danielle M.} and Francesca Ducci and Alanna Easton and Edenberg, {Howard J} and T{\~o}nu Esko and T{\~o}nu Esk and Alberto Fern{\'a}ndez-Medarde and Foroud, {Tatiana M.} 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 Khaw, {Kay Tee} and Brigitte Kuehnel and Jaana Laitinen and St{\'e}phane Lobbens and Jian'an Luan and Massimo Mangino and Matthieu Maroteaux and Giuseppe Matullo and McCarthy, {Mark I.} and Christian Mueller and Navis, {Gerjan J.} and Numans, {Mattijs E} and Alejandro N{\'u}{\~n}ez and Nyholt, {Dale R.} and Onland-Moret, {Charlotte N} and Oostra, {Ben A.} and O'Reilly, {Paul F.} and Miklos Palkovits and Penninx, {Brenda Wjh} 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 T{\"o}njes 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 H-Erich Wichmann and Gonneke Willemsen and Witteman, {Jacqueline C.} and Xin Yuan and Guangju Zhai and Zhao, {Jing Hua} and Weihua Zhang and Martin, {Nicholas G.} and Andres Metspalu and Angela Doering and James Scott and Spector, {Tim D.} and Loos, {Ruth Jf} 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 = "0027-8424",

publisher = "National Academy of Sciences",

number = "17",

}

Schumann, G, Coin, LJ, Lourdusamy, A, Charoen, P, Berger, KH, Stacey, D, Desrivières, S, Aliev, FA, Khan, AA, Amin, N, Aulchenko, YS, Bakalkin, G, Bakker, SJL, Balkau, B, Beulens, JW, Bilbao, A, de Boer, RA, Beury, D, Bots, ML, Breetvelt, EJ, Cauchi, S, Cavalcanti-Proença, C, Chambers, JC, Clarke, T-K, Dahmen, N, de Geus, EJC, DIck, DM, Ducci, F, Easton, A, Edenberg, HJ, Esko, T, Esk, T, Fernández-Medarde, A, Foroud, TM, 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, KT, Kuehnel, B, Laitinen, J, Lobbens, S, Luan, J, Mangino, M, Maroteaux, M, Matullo, G, McCarthy, MI, Mueller, C, Navis, GJ, Numans, ME, Núñez, 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, Tönjes, 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, H-E, 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 › 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, Gunter

AU - Coin, Lachlan J

AU - Lourdusamy, Anbarasu

AU - Charoen, Pimphen

AU - Berger, Karen H

AU - Stacey, David

AU - Desrivières, Sylvane

AU - Aliev, Fazil A

AU - Khan, Anokhi A

AU - Amin, Najaf

AU - Aulchenko, Yurii S.

AU - Bakalkin, Georgy

AU - Bakker, Stephan JL

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, Stéphane

AU - Cavalcanti-Proença, Christine

AU - Chambers, John C.

AU - Clarke, Toni-Kim

AU - Dahmen, Norbert

AU - de Geus, Eco J. C.

AU - DIck, Danielle M.

AU - Ducci, Francesca

AU - Easton, Alanna

AU - Edenberg, Howard J

AU - Esko, Tõnu

AU - Esk, Tõnu

AU - Fernández-Medarde, Alberto

AU - Foroud, Tatiana M.

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, Stéphane

AU - Luan, Jian'an

AU - Mangino, Massimo

AU - Maroteaux, Matthieu

AU - Matullo, Giuseppe

AU - McCarthy, Mark I.

AU - Mueller, Christian

AU - Navis, Gerjan J.

AU - Numans, Mattijs E

AU - Núñez, 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 Wjh

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 - Tönjes, 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, H-Erich

AU - Willemsen, Gonneke

AU - Witteman, Jacqueline C.

AU - Yuan, Xin

AU - Zhai, Guangju

AU - Zhao, Jing Hua

AU - Zhang, Weihua

AU - Martin, Nicholas G.

AU - Metspalu, Andres

AU - Doering, Angela

AU - Scott, James

AU - Spector, Tim D.

AU - Loos, Ruth Jf

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 ∼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.

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 ∼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.

KW - Alcohol Drinking

KW - Animals

KW - Drosophila melanogaster

KW - European Continental Ancestry Group

KW - Female

KW - Gene Expression Regulation

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Mice

KW - Nuclear Proteins

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Quantitative Trait, Heritable

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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 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

Abstract

Keywords

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