title: Genetic variation in GABRA2 moderates peer influence on externalizing behavior in adolescents.
abstract: BACKGROUND
  Genetic predisposition and environmental influences are both important factors in the development of problematic behavior leading to substance use in adolescence. Involvement with delinquent peers also strongly predicts adolescent externalizing behavior. Several lines of evidence support a role of GABRA2 on externalizing behavior related to disinhibition. However, whether this genetic association is influenced by the environment such as peer behavior remains unknown.
  
  
  METHODS
  We examined the moderating role of GABRA2 genetic variation on the socialization model of delinquent peer affiliation (at ages 12-14 years) on externalizing behavior (at ages 15-17 years) in the Michigan Longitudinal Study (MLS) adolescent sample. The sample consisted of 244 adolescents (75 females and 152 with at least one parent with a DSM-IV lifetime alcohol dependence/abuse diagnosis). Peer delinquent activity reported by the participant and teacher-reported adolescent externalizing behavior (Teacher Report Form (TRF) were assessed.
  
  
  RESULTS
  No main effect of the GABRA2 SNP rs279826, which tags a large haplotype, on externalizing behavior was observed. However, there was a statistically reliable GABRA2 × peer delinquency interaction. The effect of peer delinquent involvement on externalizing scores and the rule breaking subscale is significantly stronger for those with the GG genotype compared to A-carriers, whereas there was no effect of genotype on externalizing in the absence of peer delinquent involvement. No interaction was observed for the aggression subscale.
  
  
  CONCLUSIONS
  Our results suggest that the genetic effect of GABRA2 on externalizing behavior, more specifically on rule breaking is, at least in part, due to its effect on susceptibility to environmental exposure (i.e., peer delinquency).
authors.affiliation: Department of Psychiatry, University of Michigan Ann Arbor, Michigan ; Molecular & Behavioral Neuroscience Institute, University of Michigan Ann Arbor, Michigan.
authors.forename: Sandra
authors.initials: S
authors.lastname: Villafuerte
authors.affiliation: Department of Psychiatry, University of Michigan Ann Arbor, Michigan ; Addiction Research Center, University of Michigan Ann Arbor, Michigan.
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Trucco
authors.affiliation: Department of Psychiatry, University of Michigan Ann Arbor, Michigan ; Addiction Research Center, University of Michigan Ann Arbor, Michigan.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Heitzeg
authors.affiliation: Department of Psychiatry, University of Michigan Ann Arbor, Michigan ; Molecular & Behavioral Neuroscience Institute, University of Michigan Ann Arbor, Michigan ; Department of Human Genetics, University of Michigan Ann Arbor, Michigan ; Department of Computational Medicine and Bioinformatics, University of Michigan Ann Arbor, Michigan.
authors.forename: Margit
authors.initials: M
authors.lastname: Burmeister
authors.affiliation: Department of Psychiatry, University of Michigan Ann Arbor, Michigan ; Addiction Research Center, University of Michigan Ann Arbor, Michigan.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Zucker
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior; D000374:Aggression; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D007604:Juvenile Delinquency; D016014:Linear Models; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D011963:Receptors, GABA-A / Q000235:genetics*
chemical_list: C484841:GABRA2 protein, human; D011963:Receptors, GABA-A
keywords: Adolescence; GABRA2; externalizing; gene–environment interaction; peer delinquency