These findings also have clinical implications. Firstly, evidence of extensive genetic overlap with limited trait specificity underscores the limited extent to which our current categorical diagnostic system maps on to underlying biological processes.37 These findings may therefore be more consistent with dimensional approaches to psychiatric nosology which allow for specific combinations of symptoms as well as interactions with other mental traits, as proposed by the RDoC or HiTOP taxonomies.38,39 This may also help to explain the large degree of comorbidity and the prominence of overlapping clinical characteristics observed across mental disorders. Alternatively, once greater proportions of the SNP-based heritability of mental disorders have been characterized, it may be possible to parse the heritable component into constituent biological processes. This may enable construction of a personalised, biologically-informed diagnostic system, similar to the “palette model” proposed for diabetes.40 As the era of large-scale case control GWAS transitions towards deeply phenotyped clinical and population samples,41 it will be of great interest whether sub-phenotyping results in more specific genetic signals. This will also be highly relevant for the clinical application of polygenic risk scores, which not only require improved explained variance but also the ability to discriminate across diagnostic groups or clinically relevant decisions.
