As expected, most of the genetic effects operated via intermediate phenotypes. However, there was also evidence for two direct effects. Those with the 5-HTTLPR SS genotype had higher rates of problematic alcohol use, which maps on to prior work with youth (Merenäkk et al., 2011). Mesolimbic serotonergic pathways have been demonstrated to play a critical role in the development of alcohol dependence and ethanol tolerance (Türker et al., 1998). The short variant reduces the transcription rate of mRNA resulting in decreased 5-HTT expression and 5-HT reuptake (Lesch et al., 1996), which likely contributes to increased rates of of alcohol dependence among those carrying the s allele (Feinn, Nellissery, & Kranzler, 2005; Merenäkk et al., 2011). In addition, the s allele is associated with reduced gray matter volume in the limbic system (Canli & Lesch, 2007). In turn, findings demonstrate that reduced gray matter in the limbic system increases risk for alcohol addiction due to reward deficiencies and exaggerated processing of incentive values of substance-related stimuli (Blum et al., 2000). In addition, those with the AA genotype of SLC6A2 rs36021 had
