title: COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence.
abstract: Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, The Netherlands. a.f.a.schellekens@psy.umcn.nl
authors.forename: Arnt F A
authors.initials: AF
authors.lastname: Schellekens
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Bart
authors.initials: B
authors.lastname: Ellenbroek
authors.forename: Alexander
authors.initials: A
authors.lastname: Cools
authors.forename: Cor A J
authors.initials: CA
authors.lastname: de Jong
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.forename: Robbert-Jan
authors.initials: RJ
authors.lastname: Verkes
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D000704:Analysis of Variance; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002649:Child Abuse / Q000706:statistics & numerical data; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008016:Life Change Events; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D057566:Self Report; D012720:Severity of Illness Index; D013315:Stress, Psychological / Q000453:epidemiology / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D017448:Receptors, Dopamine D2; D008715:Methionine; D002394:Catechol O-Methyltransferase; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D014633:Valine; D004298:Dopamine