PRS explained most variance in liability in cohorts of European ancestry (again a result of the ancestry composition of the GWAS9) and in samples which by ascertainment likely include the most severe cases (hospitalised patients or those treated with clozapine) (Supplementary Note). However, even in EUR cohorts, the median Area Under the Receiver Operating Characteristic Curve (AUC) is only 0.72, meaning the liability explained is insufficient for predicting diagnosis in the general population. Nevertheless, as a quantitative estimate of liability to schizophrenia, PRS has applications in research, and in those contexts, PRS can index substantial differences in liability between individuals in the primary GWAS. Compared to the lowest centile of PRS, the highest centile of PRS has an OR for schizophrenia of 39 (95% CI=29–53), and 5.6 (CI 4.9–6.5) when the top centile is compared with the remaining 99% of individuals (Supplementary Table 6). An extended discussion of heritability and polygenic prediction is provided in the Supplementary Note.
