Study limitations are noted. First, we do not claim to have identified all the causative genetic variants; we may be detecting significant signals where there are contributions from LD with an additional untested, “true” variant (or variants), not only in ADH1B but across the ADH gene cluster. However, enzymatic studies show that the ADH1B*2 and ADH1C*2 variants are functional, affecting enzyme kinetics (Bosron et al., 1983; Bosron & Li, 1986). Next, the unique haplotype structure in this population was useful in enabling us to identify diplotypes with certainty and to categorize them into three risk groups. However, to more fully understand the joint or related interaction effects, samples with different LD patterns and greater prevalence of the rare haplotypes/diplotypes (e.g., lack of ADH1C protective allele with the presence of the ADH1B protective allele) should be studied. In addition, this study examined two genes in relation to six related alcohol outcomes in an effort to systematically assess the association. Prior evidence for genetic association, along with the high degree of correlation between the alcohol phenotypes (r2 range from 0.35-0.96) and SNPs
