In addition to low power, findings from candidate gene main effect research in psychiatry suggest that the priors in cG×E research may also be low. For one thing, candidate gene main effect studies in psychiatry have yielded no unequivocally accepted associations after more than a decade of intense efforts (10), despite the fact that candidate gene main effect hypotheses were predicated on robust neurobiological findings. In contrast, GWA studies have identified numerous replicable associations that have not usually been in candidate genes: out of 531 of the most robustly associated single-nucleotide polymorphisms (SNPs) to various medical and psychiatric phenotypes in GWA studies, 45% were in introns, 43% were in intergenic regions, and only 11% were in exons (35), the typical hunting ground for candidate polymorphisms. Furthermore, when candidate polymorphisms have been examined among GWA results, they have usually not demonstrated better than chance performance (12–15).
