On the basis of resilience and differential susceptibility theories (Belsky et al., 2007; Caspi, Hariri, Holmes, Uher, & Moffitt, 2010; Cicchetti & Blender, 2006), a G×E hypothesis about the genetic moderation of prevention effects on increases in adolescent substance use was tested. The results indicated that male adolescents who carried at least one l allele of DRD4 who were assigned to the attention control evinced more substance use over time than did (a) those who were assigned to SAAF–T or (b) adolescents assigned to either condition who carried two s alleles. These G×E effects were mediated by G×E effects on protective parenting processes. The results extend previous findings that carrying an l allele of DRD4 increases sensitivity to intervention or prevention programs among toddlers (Bakermans-Kranenburg, van IJzendoorn, Pijlman, Mesman, & Juffer, 2008), kindergarten children (Kegel, Bus, & van IJzendoorn, 2011), and 11-year-old children (Beach, Brody, Lei, & Philibert, 2010).
