Role of GABRA2 in trajectories of externalizing behavior across development and evidence of moderation by parental monitoring.

CONTEXT As we identify genes involved in psychiatric disorders, the next step will be to study how the risk associated with susceptibility genes manifests across development and in conjunction with the environment. We describe analyses aimed at characterizing the pathway of risk associated with GABRA2, a gene previously associated with adult alcohol dependence, in a community sample of children followed longitudinally from childhood through young adulthood. OBJECTIVE To test for an association between GABRA2 and trajectories of externalizing behavior from adolescence to young adulthood and for moderation of genetic effects by parental monitoring. DESIGN Data were analyzed from the Child Development Project, with yearly assessments conducted since that time. A saliva sample was collected for DNA at the 2006 follow-up, with a 93% response rate in the target sample. Growth mixture modeling was conducted using Mplus to identify trajectories of externalizing behavior and to test for effects of GABRA2 sequence variants and parental monitoring. SETTING Nashville and Knoxville, Tennessee, and Bloomington, Indiana. PARTICIPANTS A community-based sample of families enrolled at 3 sites as children entered kindergarten in 1987 and 1988. Analyses for the white subset of the sample (n = 378) are reported here. MAIN OUTCOME MEASURES Parental monitoring measured at 11 years of age; Child Behavior Checklist youth reports of externalizing behavior at ages 12, 14, 15, 16, 17, 19, 20, 21, and 22 years. RESULTS Two classes of externalizing behavior emerged: a stable high externalizing class and a moderate decreasing externalizing behavior class. The GABRA2 gene was associated with class membership, with subjects who showed persistent elevated trajectories of externalizing behavior more likely to carry the genotype previously associated with increased risk of adult alcohol dependence. A significant interaction with parental monitoring emerged; the association of GABRA2 with externalizing trajectories diminished with high levels of parental monitoring. CONCLUSIONS These analyses underscore the importance of studying genetic effects across development and of identifying environmental factors that moderate risk.