The association of ADH1C with alcohol dependence is less robust than that of ADH1B. ADH1C*2 is associated with AD and consumption in East Asians (e.g. (Thomasson et al., 1991, Thomasson et al., 1994, Matsuo et al., 2007)), where ADH1C*1 (the higher activity, protective form) is at high frequency (Table 2) and tends to travel with ADH1B*2 (higher activity, protective); D’ = 0.78 in CHB+JPT. The LD pattern led to suggestions that the evidence for an effect of ADH1C*1 independent of ADH1B*2 was weak (Osier et al., 1999, Chen et al., 1999b, Choi et al., 2005). A meta-analysis suggested that ADH1C*1 was protective (OR = 0.52) (Zintzaras et al., 2006). A later meta-analysis found stronger evidence that ADH1C*1 was protective against AD in Asians (OR = 0.47, p = 4×10−33) but was not significant in Europeans (Li et al., 2012a). Neither meta-analysis explicitly examined whether the effect was independent of ADH1B genotype.
