However, early enthusiasm for cGxE findings has waned as the number of failures to replicate original findings mounted. In many ways, the progression of cGxE studies has closely paralleled the trajectory of studies of the main effects of candidate genes, with early enthusiasm and adoption of genotyping candidate genes giving way to a literature plagued by small studies, failures to replicate, and a proliferation of novel findings with effect sizes that appeared at odds with what was subsequently found with well-powered studies (Neiswanger, Kaplan, & Hill, 1995). However, the study of genetic main effects has advanced dramatically since the early days of candidate gene research. We believe that what has been learned about the genetics of complex behavior from studies of genetic main effects yields insights into previous cGxE studies and ways to improve such research in the future. We begin by providing a broad review of developments in the field of psychiatric genetics over the past decade and discuss how this knowledge can inform studies of cGxE.
