Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis

Barbara Ruggeri; Charlotte Nymberg; Eero Vuoksimaa; Anbarasu Lourdusamy; Cybele P Wong; Fabiana M Carvalho; Tianye Jia; Anna Cattrell; Christine Macare; Tobias Banaschewski; Gareth J Barker; Arun L W Bokde; Uli Bromberg; Christian Büchel; Patricia J Conrod; Mira Fauth-Bühler; Herta Flor; Vincent Frouin; Jürgen Gallinat; Hugh Garavan; Penny Gowland; Andreas Heinz; Bernd Ittermann; Jean-Luc Martinot; Frauke Nees; Zdenka Pausova; Tomáš Paus; Marcella Rietschel; Trevor Robbins; Michael N Smolka; Rainer Spanagel; Georgy Bakalkin; Jonathan Mill; Wolfgang H Sommer; Richard J Rose; Jia Yan; Fazil Aliev; Danielle Dick; Jaakko Kaprio; Sylvane Desrivières; Gunter Schumann; IMAGEN Consortium

doi:10.1176/appi.ajp.2014.14030382

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis

Barbara Ruggeri, Charlotte Nymberg, Eero Vuoksimaa, Anbarasu Lourdusamy, Cybele P Wong, Fabiana M Carvalho, Tianye Jia, Anna Cattrell, Christine Macare, Tobias Banaschewski, Gareth J Barker, Arun L W Bokde, Uli Bromberg, Christian Büchel, Patricia J Conrod, Mira Fauth-Bühler, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh GaravanPenny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Frauke Nees, Zdenka Pausova, Tomáš Paus, Marcella Rietschel, Trevor Robbins, Michael N Smolka, Rainer Spanagel, Georgy Bakalkin, Jonathan Mill, Wolfgang H Sommer, Richard J Rose, Jia Yan, Fazil Aliev, Danielle Dick, Jaakko Kaprio, Sylvane Desrivières, Gunter Schumann, IMAGEN Consortium

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

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Abstract

OBJECTIVE: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.

METHOD: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents.

RESULTS: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task.

CONCLUSIONS: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.

Original language	English
Pages (from-to)	543-552
Number of pages	10
Journal	The American Journal of Psychiatry
Volume	172
Issue number	6
Early online date	18 May 2015
DOIs	https://doi.org/10.1176/appi.ajp.2014.14030382
Publication status	Published - 1 Jun 2015

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10.1176/appi.ajp.2014.14030382

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Ruggeri, B., Nymberg, C., Vuoksimaa, E., Lourdusamy, A., Wong, C. P., Carvalho, F. M., Jia, T., Cattrell, A., Macare, C., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Bromberg, U., Büchel, C., Conrod, P. J., Fauth-Bühler, M., Flor, H., Frouin, V., Gallinat, J., ... IMAGEN Consortium (2015). Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis. The American Journal of Psychiatry, 172(6), 543-552. https://doi.org/10.1176/appi.ajp.2014.14030382

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title = "Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis",

abstract = "OBJECTIVE: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.METHOD: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents.RESULTS: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task.CONCLUSIONS: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.",

author = "Barbara Ruggeri and Charlotte Nymberg and Eero Vuoksimaa and Anbarasu Lourdusamy and Wong, {Cybele P} and Carvalho, {Fabiana M} and Tianye Jia and Anna Cattrell and Christine Macare and Tobias Banaschewski and Barker, {Gareth J} and Bokde, {Arun L W} and Uli Bromberg and Christian B{\"u}chel and Conrod, {Patricia J} and Mira Fauth-B{\"u}hler and Herta Flor and Vincent Frouin and J{\"u}rgen Gallinat and Hugh Garavan and Penny Gowland and Andreas Heinz and Bernd Ittermann and Jean-Luc Martinot and Frauke Nees and Zdenka Pausova and Tom{\'a}{\v s} Paus and Marcella Rietschel and Trevor Robbins and Smolka, {Michael N} and Rainer Spanagel and Georgy Bakalkin and Jonathan Mill and Sommer, {Wolfgang H} and Rose, {Richard J} and Jia Yan and Fazil Aliev and Danielle Dick and Jaakko Kaprio and Sylvane Desrivi{\`e}res and Gunter Schumann and {IMAGEN Consortium}",

year = "2015",

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doi = "10.1176/appi.ajp.2014.14030382",

language = "English",

volume = "172",

pages = "543--552",

journal = "The American Journal of Psychiatry",

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Ruggeri, B , Nymberg, C, Vuoksimaa, E, Lourdusamy, A , Wong, CP, Carvalho, FM, Jia, T , Cattrell, A , Macare, C, Banaschewski, T, Barker, GJ, Bokde, ALW, Bromberg, U, Büchel, C, Conrod, PJ, Fauth-Bühler, M, Flor, H, Frouin, V, Gallinat, J, Garavan, H, Gowland, P, Heinz, A, Ittermann, B, Martinot, J-L, Nees, F, Pausova, Z, Paus, T, Rietschel, M, Robbins, T, Smolka, MN, Spanagel, R, Bakalkin, G, Mill, J, Sommer, WH, Rose, RJ, Yan, J, Aliev, F, Dick, D, Kaprio, J, Desrivières, S , Schumann, G & IMAGEN Consortium 2015, 'Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis', The American Journal of Psychiatry, vol. 172, no. 6, pp. 543-552. https://doi.org/10.1176/appi.ajp.2014.14030382

TY - JOUR

T1 - Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis

AU - Ruggeri, Barbara

AU - Nymberg, Charlotte

AU - Vuoksimaa, Eero

AU - Lourdusamy, Anbarasu

AU - Wong, Cybele P

AU - Carvalho, Fabiana M

AU - Jia, Tianye

AU - Cattrell, Anna

AU - Macare, Christine

AU - Banaschewski, Tobias

AU - Barker, Gareth J

AU - Bokde, Arun L W

AU - Bromberg, Uli

AU - Büchel, Christian

AU - Conrod, Patricia J

AU - Fauth-Bühler, Mira

AU - Flor, Herta

AU - Frouin, Vincent

AU - Gallinat, Jürgen

AU - Garavan, Hugh

AU - Gowland, Penny

AU - Heinz, Andreas

AU - Ittermann, Bernd

AU - Martinot, Jean-Luc

AU - Nees, Frauke

AU - Pausova, Zdenka

AU - Paus, Tomáš

AU - Rietschel, Marcella

AU - Robbins, Trevor

AU - Smolka, Michael N

AU - Spanagel, Rainer

AU - Bakalkin, Georgy

AU - Mill, Jonathan

AU - Sommer, Wolfgang H

AU - Rose, Richard J

AU - Yan, Jia

AU - Aliev, Fazil

AU - Dick, Danielle

AU - Kaprio, Jaakko

AU - Desrivières, Sylvane

AU - Schumann, Gunter

AU - IMAGEN Consortium

PY - 2015/6/1

Y1 - 2015/6/1

N2 - OBJECTIVE: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.METHOD: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents.RESULTS: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task.CONCLUSIONS: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.

AB - OBJECTIVE: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.METHOD: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents.RESULTS: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task.CONCLUSIONS: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.

U2 - 10.1176/appi.ajp.2014.14030382

DO - 10.1176/appi.ajp.2014.14030382

M3 - Article

C2 - 25982659

SN - 0002-953X

VL - 172

SP - 543

EP - 552

JO - The American Journal of Psychiatry

JF - The American Journal of Psychiatry

IS - 6

ER -

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis

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