PRS for BD explained on average 4.57% of phenotypic variance (liability scale) across European cohorts, although this varied in different waves of the BD GWAS, ranging from 6.6% in the PGC1 cohorts to 2.9% in the External biobank studies (Supplementary Fig. 7 and Supplementary Table 12). These results are in line with the hSNP2 of BD per wave, which ranged from 24.6% (s.e. =0.01) in PGC1 to 11.9% (s.e. = 0.01) in External studies (Supplementary Table 3). Some variability in hSNP2 estimates may arise from the inclusion of cases from population biobanks, who may have more heterogeneous clinical presentations or less severe illness than BD patients ascertained via inpatient or outpatient psychiatric clinics. Across the waves of clinically ascertained samples within the PGC, hSNP2 and the R2 of PRS also varied, likely reflecting clinical and genetic heterogeneity in the type 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
