Despite numerous positive reports of cG×Es in the psychiatric genetics literature, our findings underscore several concerns that have been raised about the cG×E field in psychiatry. Our results suggest the existence of a strong publication bias toward positive findings that makes cG×E findings appear more robust than they actually are. Almost all novel results are positive, compared with less than one-third of replication attempts. More troubling is evidence suggesting that replication studies, generally considered the sine qua non of scientific progress, are also biased toward positive results. Furthermore, it appears that sample sizes for null replication results must be approximately six times larger than sample sizes for positive replication results in order to be deemed publishable on their own. Such a publication bias among replication attempts suggests that meta-analyses, which collapse across replication results for a given cG×E hypothesis, will also be biased toward being unrealistically positive. Although methods exist to detect publication biases (e.g., the funnel plot), they are not very sensitive, and correcting meta-analytic results for this bias is difficult (41). Finally, our findings suggest that meta-analyses using very liberal inclusion thresholds (e.g., Karg et al. [39]) are virtually guaranteed to find positive results.
