of BD cases ascertained; the PGC1 cohorts consisted mostly of BD I cases9, known to be the most heritable of the BD subtypes11,24, while later waves included more individuals with BD II24. Overall, the hSNP2 of BD calculated from the meta-analysis summary statistics was 18% on the liability scale, a decrease of ~2% compared with the PGC2 GWAS24, which may be due to the addition of cohorts with lower hSNP2 estimates and heterogeneity between cohorts (Supplementary Table 3). However, despite differences in hSNP2 and R2 of PRS per wave, the genetic correlation of BD between all waves was high (weighted mean rg = 0.94, s.e. = 0.03), supporting our rationale for combining cases with different BD subtypes or ascertainment to increase power for discovery of risk variants. In Europeans, individuals in the top 10% of PRS had an OR of 3.5 for BD, compared with individuals with average PRS (middle decile), which translates into a modest absolute lifetime risk of the disorder (7% based on PRS alone). While PRS are invaluable tools in research settings, the current BD PRS lack sufficient power to separate individuals into clinically meaningful risk categories, and therefore have no clinical utility at present87,88. PRS from
