Consistent with Schuckit’s research, findings from the AACTS suggest that men who inherit a low reactivity to alcohol have an increased risk of alcohol dependence. Currently, we do not know which genes are involved in this reduced reactivity to alcohol. Genetic variations (i.e., polymorphisms) in a key enzyme involved in alcohol metabolism (i.e., alcohol dehydrogenase) at two genes called ADH2 and ADH3 did not predict differences in alcohol reactivity, even though the ADH2*2 gene variant (i.e., allele) predicted diminished alcohol-dependence risk in men from this sample (Whitfield et al. 1998). However, analyses of the relationship between smoking history and alcohol challenge performance produced important further insights. Men and women who were current smokers at the time of the alcohol challenge study rated themselves as significantly less intoxicated than did nonsmokers or former smokers despite receiving the same amount of alcohol (Madden et al. 1995). This relationship persisted in women, even when a history of heavy drinking was controlled for, and also was observed in men at the second post-alcohol assessment. Furthermore, in women, researchers found a highly significant genetic correlation
