Understanding the joint effects of these variants on alcohol use behavior is important. Numerous studies have examined interaction effects between ADH genes in East Asians (Wu et al., 2012), but only three studies have explicitly examined the joint effect of ADH1B-rs1229984 and ADH1C-rs698 on alcohol outcomes in non-Asian populations (Neumark et al., 2004; Tolstrup et al., 2008; Toth et al., 2011). While all three studies showed an effect of ADH1B on alcohol-related phenotypes, only one study found an effect of ADH1C on alcohol-related phenotypes (alcohol problems) as well as a joint effect of ADH1B and ADH1C (Toth et al., 2011). These studies varied in many respects, including ancestry and genotype frequencies, phenotypes, and methods of testing interaction between ADH1B and ADH1C SNPs, leaving the cumulative interpretation unclear. Therefore, investigating the joint effects of ADH1B and ADH1C on alcohol phenotypes (DSM-IV AUDs, consumption) in large samples with sufficient power remains necessary.
