Several limitations need to be considered when interpreting the results. These models accounted for a modest amount of the total variance in substance use. Moreover, the five genetic factors included in the current study collectively explained approximately 1.5% of the variance in substance use. Yet, models included multiple informants and prospective effects across development. Although this provides a stronger methodological approach, it likely contributes to the lower effect sizes. Taken together, this indicates that other pathways to substance use exist. In addition, numerous variants across the dopaminergic, GABAergic, glutamatergic, opiod, cholinergic, and serotonergic neurotransmitter systems have demonstrated associations with substance use, addiction, and alcohol metabolism (see Köhnke, 2008 for a review). We focused on a small number of these genetic markers, which likely contributes to a smaller explained variance. Similarly, although our sample size is comparable to other studies examining mediated effects of genes on substance use (e.g., Laucht et al., 2007), it precluded us from examining polygenic effects. Given that complex behaviors are known to be a result of multiple genetic effects it will be important that future studies
