With respect to mechanisms for this effect, Pierucci-Lagha et al. (2005) and Haughey et al. (2008) have proposed that increased risk for alcohol dependence may be due to GABRA2 moderating the subjective effects of alcohol (an individual's susceptibility to intoxication). Other evidence suggests that GABRA2 may contribute to a common underlying genetic vulnerability to alcohol and drug dependence. It is known from twin studies that there are shared genetic risk factors between alcohol and nicotine dependence (Madden et al., 2000; True et al., 1999) as well as alcohol and drug dependence (Kendler et al., 2003). The COGA group recently reported an association between GABRA2 and drug dependence, including illicit drugs and cannabis (Agrawal et al., 2006). Importantly, subsequent analysis of the COGA dataset showed that the initial association between GABRA2 and AD was primarily driven by those individuals with co-occurring illicit drug dependence and when those individuals were excluded, evidence for association with AD disappeared (Agrawal et al., 2006). In contrast, excluding European American AD cases comorbid for drug (cocaine and/or opioid) dependence increased the strength of association between GABRA2
