an individual at very high genetic risk, the PRS signal would be overpowered by the unmodelled component. Depression PRS is therefore not yet useful, and any future utility would be based on substantially increasing the variance explained by the PRS or by joint modelling of genetic and environmental risk factors. Increasing the sample size with the inclusion of broader self-reported definitions of depression [55] resulted in a modest increase of the variance explained by PRS, albeit at the cost of specificity for major depression. Phenotypic refinement has been proposed as an alternative to produce more clinically relevant findings [56].
