In Chinese subjects from rural Northern Hunan Province ALDH2*2 was associated with flushing (p=4.8 ×10−26), reduced the number of maxdrinks (p = 1.5 ×10−16), and was protective against alcohol dependence (p=4.7 ×10−8) (Quillen et al., 2014). SNPs in nearby genes also appeared to be associated (Supplementary Table 2), due to the extensive LD in the region (D’ between rs671 and many SNPs across 1 Mb is over 0.6; Supplementary Figure 3): conditioning on rs671 did not leave any others significant, including a previously reported association in CCDC63 (Quillen et al., 2014). ALDH2*2 explained a substantial fraction of the total phenotypic variance, 7.9% for AD, 22.9% for maxdrinks and 29.3% for flushing (Quillen et al., 2014). Women in that study had very low levels of alcohol consumption, so analyses of women had little or no power. A GWAS on a small number of Korean men found rs671 was associated with alcohol dependence (p = 8.4 ×10−8; OR = 0.22) (Park et al., 2013). A recent GWAS in Thai subjects (ascertained for methamphetamine dependence or use) gave similar results: significant association of rs671 with flushing (5.2×10−14), maxdrinks (1.3×10−10) and DSM-IV criterion count (4.5 ×10−9) (Gelernter et al., 2018).
