PRS studies have been especially abundant in schizophrenia, where GWAS sample sizes have thus far been the largest (11). For example, family history, socioeconomic status, and PRS explain a similar fraction of overall schizophrenia risk, with family history mediated partially through PRS (79). PRS that predict psychiatric disorder risk are associated with behavioral and cognitive differences in the general population among individuals that are typically referred to as ‘controls’ (69). High schizophrenia PRS is associated with higher childhood cognitive, social, behavioral, and emotional impairments, although the great majority of children exhibiting such deficits do not later develop schizophrenia (80). Among diagnosed schizophrenia patients, outcomes such as chronicity and hospital admission rates have also been significantly correlated with schizophrenia PRS, although chronic readmission could bias ascertainment in GWAS (81). Other cognitive phenotypes are also associated with schizophrenia risk, including lower IQ and educational attainment, and higher creativity (82–84). Geographical risk from serial founder effects are correlated with elevated schizophrenia risk in northern Finland (85–87), although additional work is needed to disentangle the role of population structure (56).
