While prior studies have examined gene-gene interactions between ADH genes (Wu et al., 2012), only three studies explicitly examined the joint effect of these specific ADH SNPs for alcohol outcomes (Neumark et al., 2004; Tolstrup et al., 2008; Toth et al., 2011). Results from these studies were mixed; the Neumark study found no evidence of interaction between these two SNPs, while the more recent studies indicated that the joint effects of these ADH risk alleles (using haplotypes/diplotypes) increased risk for excessive consumption and AUDs (Tolstrup et al., 2008; Toth et al., 2011). Results from our study can potentially clarify these discrepancies in that we found the joint effect (of both ADH1B and ADH1C) is related to AUDs, but not significantly to measures of consumption in this large population of Israeli Jews. While a genetic variant could plausibly be consistently associated with all related phenotypes (consumption and AUDs), that is not necessarily the case if different measures tap into different aspects of a related phenotype which may have unique etiological risk factors (Meyers et al., 2012). Further studies are needed to examine the association of AUDs and consumption with ADH1C.
