of variants significant in follow-up is close to expectation (8 observed with follow-up p<0.05, 8.26 expected, Poisson binomial p = 0.57), and that 11 variants achieving genome-wide significance in the combined analysis is also within the expected range (p = 0.29). As an alternative to winner’s curse correction, we conducted a polygenic inference analysis using a mixture of Gaussian effect size distributions to model BD genetic architecture and estimate the variants’ true effect sizes 29 (Supplementary Note, Supplementary Figure 5). Under this model, we found that only two variants were nominally significantly weaker in follow-up than expected by chance (TRANK1 rs9834970 p = 0.012, and rs13821 p = 0.026; Supplementary Table 7), and none were Bonferroni significant (p>0.05/19=0.0026). Thus, the overall replication rate is within the expected range given the polygenic architecture of BD.
