Because early onset of alcoholism often reflects greater severity, including a higher risk for antisocial personality disorder and conduct disorder (Dick et al., 2007), and some of our earlier findings were stronger with this sub-phenotype (Agrawal et al., 2006; Dick et al., 2007; Edenberg et al., 2008), we examined whether the findings were primarily due to the cases with early onset. This was, in fact, found: eighteen SNPs spread across the 2-gene cluster, including a synonymous coding SNP (rs282117; Val83) in GABRR2, were significantly associated with early onset alcohol dependence. The increase in evidence for association despite the reduction by nearly half in the number of individuals deemed affected in this analysis suggests that the association with alcohol dependence is particularly strong in individuals who developed alcoholism at age 21 or younger.
