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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Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis. / Ruggeri, Barbara; Nymberg, Charlotte; Vuoksimaa, Eero; Lourdusamy, Anbarasu; Wong, Cybele P; Carvalho, Fabiana M; Jia, Tianye; Cattrell, Anna; Macare, Christine; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia J; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Nees, Frauke; Pausova, Zdenka; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor; Smolka, Michael N; Spanagel, Rainer; Bakalkin, Georgy; Mill, Jonathan; Sommer, Wolfgang H; Rose, Richard J; Yan, Jia; Aliev, Fazil; Dick, Danielle; Kaprio, Jaakko; Desrivières, Sylvane; Schumann, Gunter; IMAGEN Consortium.
in: AM J PSYCHIAT, Jahrgang 172, Nr. 6, 06.2015, S. 543-52.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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
Y1 - 2015/6
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.
KW - Adolescent
KW - Alcohol-Related Disorders
KW - Alcoholism
KW - DNA Methylation
KW - Diseases in Twins
KW - Epigenesis, Genetic
KW - Female
KW - Finland
KW - Gene Expression Regulation
KW - Genetic Markers
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Impulsive Behavior
KW - Internal-External Control
KW - Male
KW - Mental Disorders
KW - Oxygen
KW - Phosphoprotein Phosphatases
KW - Subthalamic Nucleus
KW - Twins, Monozygotic
KW - Young Adult
U2 - 10.1176/appi.ajp.2014.14030382
DO - 10.1176/appi.ajp.2014.14030382
M3 - SCORING: Journal article
C2 - 25982659
VL - 172
SP - 543
EP - 552
JO - AM J PSYCHIAT
JF - AM J PSYCHIAT
SN - 0002-953X
IS - 6
ER -