Previous studies have shown that risk profile scores (RPS) constructed from alleles showing modest association with schizophrenia in a discovery GWAS can predict case-control status in independent samples, albeit with low sensitivity and specificity.10,11,16 This finding was robustly confirmed in the present study. The estimate of Nagelkerke R2 (a measure of variance in case-control status explained) depends on the specific target dataset and threshold (PT) for selecting risk alleles for RPS analysis (Extended Data Figure 5 & 6a). However, using the same target sample as earlier studies and PT =0.05, R2 is now increased from 0.03 (reference10) to 0.184 (Extended Data Figure 5). Assuming a liability-threshold model, a lifetime risk of 1%, independent SNP effects, and adjusting for case-control ascertainment, RPS now explains about 7% of variation on the liability scale46 to schizophrenia across the samples (Extended Data Figure 6b), about half of which (3.4%) is explained by genome-wide significant loci.
