, 2002 and Noble, 2003). For DRD4, it has been suggested that Wnt activation carrying the 7R allele is particularly associated with one’s likelihood to experience craving for alcohol, rather than with more general alcohol phenotypes

(Hutchison et al., 2002). A second important issue involves the reference groups used, e.g. those adolescents that did not use alcohol or cannabis. By comparing regular users to abstainers, we tried to minimize the possibility that alcohol- or cannabis use related phenotypes were included in the comparison groups. However, because genetic effects on dopamine functioning have been associated with a broad range of reward-related disorders (Hyman et al., 2006), the absence of significant differences between regular users and abstainers

might be due to the inclusion of adolescents with selleck chemicals llc reward-related phenotypes in the comparison groups. However, Sakai and colleagues assessed the direct effect of DRD2 TaqIA on early onset alcohol use disorders in an adolescent sample with a high prevalence of comorbid cannabis use disorder and conduct disorder. Even when controls were selected for the absence of other substance use disorders and conduct disorder, no significant association between the A1 allele and early onset alcohol disorder was found (Sakai et al., 2007). We hypothesized that the effects of parenting would be moderated by the effects of the genetic risk markers in DRD2 and DRD4, in a way that adolescent carriers of these risk markers would be most vulnerable to the influence of less optimal parenting. We did not find support for this hypothesis. Except for an inverse and surprising association between L-DRD4 and parental not emotional warmth, indicating that higher levels of emotional warmth are associated with an increased risk of regular alcohol use in carriers of the L-DRD4,

parenting did not moderate the actual expression of a genetic predisposition in regular alcohol or cannabis use. While we do not know about previous studies reporting on these specific gene by parenting interactions with respect to cannabis use, findings by van der Zwaluw et al. indicate that low parental rule-setting towards alcohol consumption is associated with more alcohol use over time, particularly in adolescents that carry the A1 allele (van der Zwaluw et al., 2009). This inconsistency with our findings might be explained by the difference between the studies in alcohol-related phenotypes used (regular alcohol use versus frequency of alcohol consumption). Alternatively, we suggest that substance-specific rule-setting might be more strongly associated with subsequent adolescent substance use when compared to general parenting behaviors, and might therefore more easily trigger the actual expression of a genetic predisposition. Nonetheless, our findings did provide support for risk enhancing effects of parental rejection and overprotection, and a risk buffering effect of emotional warmth.