The pattern of our results (in which pairs of disorders demonstrated genetic overlap) was consistent with polygenic profile score32 results from PGC cross-disorder analyses25. The profile score method uses SNP associations from one disorder to construct a linear predictor in another disorder. The profile scores explained small but significant proportions of the variance25, expressed as Nagelkerke’s R2 (maximum of 2.5% between schizophrenia and bipolar disorder). To achieve high R2 values requires accurate estimation of the effect sizes of individual SNPs and depends on the size of the discovery sample. In contrast, our approach uses SNPs to estimate genome-wide similarities between pairs of individuals, resulting in unbiased estimates of the relationships between disorders, with larger sample sizes generating smaller standard errors for the estimates. Our estimates were on the liability scale, allowing direct comparison to genetic parameters estimated in family studies, whereas a genetic interpretation of Nagelkerke’s R2 values is less straightforward33.
