We have previously found that the associations of GABRA2, CHRM2, and NFKB1 with alcoholism were strongest in the half of the sample that included the most severely affected individuals, whose onset of alcohol dependence was at age 21 or younger (Agrawal et al., 2006; Dick et al., 2007; Edenberg et al., 2008). Therefore, we performed additional analysis using a median split for age of onset of alcohol dependence, defining affected individuals as those who met DSM-IV criteria for alcohol dependence at age 21 or earlier (n = 399). Despite the reduction in power due to the substantially lower number of affected individuals, greater evidence for association was observed, with 16 significantly associated SNPs (p ≤ 0.05) in the GABRR1 and GABRR2 gene cluster, including a synonymous SNP (Val83; rs282117) in GABRR2, and another 8 suggestive (0.05 < p ≤ 0.10; Table 2, Figure 2).
