modest evidence of statistical epistatic effects on AD in the human literature, possibly because of a lack of power in most studies. In a recent study, Kumar et al. discovered epistatic effects between the mu and kappa opioid system, with respect to alcohol (Kumar et al., 2012). The researchers showed that although individual markers were not associated with alcoholism, locus-locus interactions between OPRM1 and OPRK1 led to a two-fold increase [2.318 (1.025 to 5.24)] in the risk for alcoholism. Coupled with findings from complex diseases, these results suggest that genetic interactions may be far more important than initially thought. Furthermore, it has been suggested that the failure to model epistatic effects in biometrical studies may have inflated the heritability of complex traits (Zuk et al., 2012). The inherent problem with capturing epistatic effects using variants with modest effect sizes arises from the vast number of possible combinations that can exist within the human genome. For example, a model containing two SNPs, each with three genotypes (i.e., AA, Aa, and aa), would have nine possible genotypes, while a model containing four SNPs would have 81 possible genotypes (i.e., 3# of SNPs). Capturing epistatic effects is further complicated by the fact that
