Larger GWAS sample sizes have also revealed extensive shared genetic risk variants across diagnostic categories, mirroring their overlapping clinical characteristics.7 A meta-analysis of eight mental disorders identified 109 independent genetic loci associated with two or more disorders.8 Interestingly, 11 of these had “discordant” effects, i.e. increased the risk of one disorder but decreased the risk of a second.8 This is supported by findings from pair-wise analyses,9,10 which have identified hundreds of shared loci between mental disorders and related traits such as intelligence11,12 and personality traits,13 with a mixture of concordant and discordant effects (fig. 1a). Such extensive “pleiotropy” calls into question the traditional conceptualisation of genetic risk, in which a specific set of genes are implicated for a specific disorder.14
