The ΔF analysis of genes with AD GWAS ancestry-specific significant alleles showed the strong diversity of ADH1B and ADH1C variation between Asian and non-Asian populations. Previous studies indicated that ADH1B-ADH1C genetic diversity between Asians and non-Asians is due in part to a selective pressure [44–46], suggesting a potential effect on ADH-associated traits, such as AD. A recent GWAS on AD traits in a Chinese study population indicated that ADH1B and ADH1C did not contain alleles significantly associated with AD traits, but ALDH2, another alcohol metabolism-related gene and an interactive partner of both ADH1B and ADH1C, showed AD risk alleles consistent with many prior observations [47]. This difference between non-Asian ancestries (i.e., AAs and EAs: genome-wide significance of ADH genes for AD traits) and Asian one (non-genome-wide significance of ADH genes for AD traits) may ultimately be attributable to the effect of natural selection on genetic variation of ADH-gene cluster.
