influence on parental behaviors that impact the offspring (Coop & Pickrell 2016). Additionally, GWAS studies of psychiatric phenotypes typically do not screen affected cases on the presence of other medical conditions (and vice-versa), thus over-representation of a given phenotype in the sample of another phenotype could bias the data toward the detection of a genetic correlation. Finally, estimates of genetic similarities could be influenced by misdiagnosed cases (Wray et al. 2012). Other general limitations of this method (in comparison with other approaches) have been discussed previously elsewhere (B. Bulik-Sullivan et al. 2015; Anttila et al. 2016). In light of the exploratory nature of the present study, another critique pertains to the lack of clearly identified positive and negative control comparisons. Additionally, the clinical significance of weak or modest genetic correlations is yet unclear. Future work could shed light on this topic by comparing the strength of reported genetic correlations with estimates of effect size from epidemiological associations, in order to create an atlas of concordance and shed light on the sensitivity and specificity of these genetic methods. One final critique of this approach is that it falls short of identifying plausible genetic and biological mechanisms that mediate potentially pleiotropic loci.
