In a family-based study that used the pedigree disequilibrium test, 12 SNPs in and near ADH4 were associated with DSM-IV-defined alcohol dependence in European American families; the top SNP was rs4148886 (Edenberg et al., 2006). Eleven of the SNPs are in LD and mark a region from intron 1 past the 3’ untranslated region that contains many additional SNPs (Edenberg et al., 2006). Neither of 2 non-synonymous SNPs, rs1126671 and rs1126673 nor a functional promoter SNP, rs1800759 (Edenberg et al., 1999) were significant, although rs1800759 had been in an earlier study in Brazil (Guindalini et al., 2005). None of a set of 7 SNPs (in nearly complete LD) showed significant association, but deviation from Hardy-Weinberg equilibrium in European Americans suggested a recessive effect; there was no evidence for association in African Americans (Luo et al., 2006a). In the Irish, there was no association of ADH4 with AD (Kuo et al., 2008). A rare variant downstream of ADH4 (rs187709743) was associated with symptom count in American Indians (Peng et al., 2017). An Australian study found suggestive evidence for association of rs1800759
