Seven ADH genes are known to exist in humans. Of these, class I gene products (ADH1A, ADH1B, and ADH1C) account for most of the capacity of the liver for ethanol oxidation. High LD has been reported for several variants across these genes (Edenberg 2007). The top SNP of the present study is located between the ADH1B and ADH1C genes. This is in complete LD (D′=1.0, r2=0.27, HapMap rel 24 CEU) with rs1693482 (Arg272Gln), a common functional amino acid substitution in the ADH1C gene. An Australian study found that Arg272Gln was associated with “amount of alcohol consumption” (Macgregor et al. 2008). This finding is compatible with the hypothesis that increased ADH activity may be protective against AD. Since Arg272Gln was not present in our data set, it was necessary to impute this marker. Based on the imputed genotypes, the higher-function 272Arg variant (Edenberg 2007) corresponding to the protective allele C of rs1789891 in the present GWAS was indeed found to be the protective allele in our sample. However, the association with Arg272Gln, (p=1.24E-7, OR=1.31) was not stronger than the association with
