Emerging evidence provides a potential clue to the mechanisms through which genes increase risk for AUD. For example, variations of the GABRA2 gene have been linked to conduct disorder in a high-risk sample of offspring of alcoholics (Dick et al. 2006). These results have recently been replicated in an independent sample of offspring from multiplex families for alcohol dependence (Hill et al. unpublished results). This suggests that GABA receptors are important for the behavioral attributes associated with externalizing disorders that may increase the likelihood of developing an AUD in young adulthood. Additionally, analyses of the COGA data indicate that the GABRA2 gene is associated with EEG oscillations and alcohol dependence, suggesting GABRA2 might influence susceptibility to alcohol dependence by modulating neural inhibition (Edenberg et al. 2004). Lastly, Hill et al. (2009a) were the first to report a statistically significant association between variation of the serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) genes and volume of the OFC in the right hemisphere among high risk offspring. Therefore, variations in genes are likely to influence behavioral outcome by altering the structure and function of specific brain systems.
