To determine polygenic enrichment between pairs of phenotypes, we used conditional quantile-quantile plots (Supplementary Figure 1), which show the distribution of p-values for one phenotype conditioning on p-value cut-offs of another phenotype (p<0.1, p<0.01, p<0.001). Four complex LD regions (Supplementary Methods) were excluded from analysis to avoid potential inflation. Identification of shared loci between pairs of phenotypes was estimated using a conjunctional FDR (conjFDR) analysis.29 This method relies on two runs of a conditional FDR (condFDR) analysis. First, the association between variants and a secondary phenotype is used to re-rank the test statistic in the primary phenotype. The process is then repeated switching the roles of the primary and secondary phenotypes. The largest condFDR value between the two runs is then used as the conjFDR value. A SNP with a conjFDR<0.05 was considered as a shared SNP.30–32 Details for conjFDR, locus definition, lead SNP identification, and SNP sign tests are provided in Supplementary Methods.
