that the “null” rs671 allele has a nearly dominant effect (Lai et al., 2014, Crabb et al., 1989); the heterozygote retains only about 17% enzyme activity compared to common-allele heterozygotes; minor-allele homozygotes had nearly nil measurable enzyme activity. We did not observe a significant association between ADH1B variants and any of the alcohol-related traits, but this may be attributable to lack of power: acceptable genotype data for that locus was available only for Sample 2 (510 subjects), and in that sample, we did observe a nominally-significant association (p = 2.72 × 10−5). Since acetaldehyde is implicated in various digestive tract cancers as well, these results may be relevant to a range of pathologies beyond AD per se. For example, this same variant is strongly implicated in esophageal cancer (Brooks et al., 2009) and head and neck cancers (Chang et al., 2017). We showed in a previous phenomewide association study (Polimanti et al., 2016) that ALDH2 rs671 is also nominally associated with “highest grade finished in school,” consistent with findings for ADH1B.
