Although multiple kinds of evidence strongly indicate that evolutionary pressures shaped ADH1B genetic diversity, the mechanisms are not well understood. Although some authors suggest it is due to the concomitant occurrence of ADH1B rs1229984 and rice domestication (and the consequent use of rice-fermented beverages) [Peng and others 2010], the protective effect of ADH1B on alcoholism, a “modern” phenotypic trait, is unlikely to be the force responsible for the selection of ADH1B rs1229984, especially since ADH1B rs1229984 expansion and selection seem to be more recent than rice domestication (rice domestication: 10,000~7,000 years ago; ADH1B rs1229984 expansion: 2,800 years ago) [Li and others 2011b]. A recent study demonstrated that ALDH2 rs671, the other locus associated with increased acetaldehyde levels in Asians [Kang and others 2014], is also associated with reduced risk of tuberculosis [Park and others 2014]. Although in the same study no association was found between tuberculosis and ADH1B and there is no genome-wide evidence for natural selection at the ALDH2 locus, this finding may suggest a role of alcohol-metabolism genes in the predisposition to infectious diseases, which are the most-recognized
