The estimates of SNP-based genetic correlation (rg SNP) between disorders reflect the genome-wide pleiotropy of variants tagged by common SNPs, and whether these are the same as correlations across the allelic frequency spectrum may differ between pairs of disorders. For example, a high rg SNP value but a low genetic correlation estimated from family studies (rg) could indicate that the same common variants contribute to genetic susceptibility for both disorders, although the diagnostic-specific variants are less common variants. For this reason, the comparison of rg SNP with rg estimated from family studies is not straightforward. Nonetheless, we benchmark our estimates in this way, calculating the increased risk of disorder B in first-degree relatives of probands with disorder A (λA,B) from the rg SNP value to allow comparison with literature values (Supplementary Table 1). A meta-analysis53 reported increased risk of bipolar disorder in first-degree relatives of probands with schizophrenia compared to first-degree relatives of control probands (λSCZ,BPD) of 2.1, which implies a maximum genetic correlation between the disorders of 0.3 (assuming that the disorder risks for schizophrenia and bipolar disorder are
