As heritability can be moderated by changing environmental exposure, genotype may only influence behavior in certain environmental milieux. Some of the earliest, most influential – and arguably most controversial – work demonstrating the importance of measured gene by environment interaction was reported by Caspi et al94 who found that a functional polymorphism in the promoter region of the serotonin transporter (5-HTT/SLC6A4) gene moderated the influence of stressful life events on depression. While these results have been subject to multiple attempts at replication with mixed results (see reviews by Merikangas95 and Caspi96), they have been highly influential in alerting the field to the possibility and promise of gene by environment interactions in the etiology of psychiatric and substance use disorders. In the study of environmental moderation of genotypic risk for substance involvement, Dick et al97 recently explored the potential moderating influence of parental monitoring on the association between GABRA2 and a broad measure of externalizing behaviors in a longitudinal sample of adolescents. Although their analyses did not focus on alcohol or other drug use, their finding that the association of GABRA2 with externalizing trajectories diminished with high levels of parental monitoring, clearly parallel the findings above.
