partially dictated by the published literature that we are reviewing. It is easy to imagine that biological pathways could also be used such that interacting neigh bors of an implicated gene might also be investigated in the complimentary species; as we discussed above, the identification of Alk in flies illustrates this concept (Lasek et al. 2011b). Interactions among genes that belong to a common pathway offer one possible explanation for the small effects of SNPs identified by GWAS relative to the large estimates of heritability (Manolio et al. 2009). This so-called `missing heritability' or `dark matter' has yet to be fully explained. One possibility is a significant portion of trait heritability results from epistatic interactions between genes. Recent studies have investigated this possibility and have identified evidence for interactions among genes. For example, Nikolova et al. (2011) computed a multi-locus genetic profile score that represented the cumulative impact of five functional polymorphic loci on DA signaling and used this profile to identify reward-related activation of the ventral striatum even though none of the loci had significant main effects. Similarly, Grucza et al. (2010) identified interactions among over 300 candidate genes as well as age of onset of smoking to identify
