Given the two-stage process of alcohol metabolism and the potential for differences in metabolic rates in one stage to be masked or heightened by rate differences in the other, we also tested for pairwise interactions between SNPs. The strongest interaction effect was between two SNPs in ADH7 that jointly predict more DSM-IV dependence criteria endorsed for each additional minor allele when at least one minor allele is present at each locus (βinteraction = 0.7, P = 0.00002). Two SNPs in high LD in ADH1B show epistatic effects with a SNP in ALDH6A1 as well (βinteraction = −0.4, P = 0.00004). Table 2 shows the epistatic effects between SNP pairs with interaction term P-values < 0.001. Although we show results for each SNP pair with interaction term P-values below this threshold, not all of these findings are independent due to high correlation between the SNPs involved (see supplementary figure 1).
