Analyzing the GWAS meta-analysis by LD score regression (LDsc)37 produced a genomic inflation factor (λGC) estimate of 1.89 with an intercept of 1.06 (SE=0.01) and an attenuation ratio of 0.047 (SE=0.012) (Supplementary Table S3), indicating that 95% of the observed inflation of the test statistics (Supplementary Figure S5) is due to a polygenic signal rather than population structure. The individual GWASs (iPSYCH2015, Howard et al. 201914, Wray et al. 201812, Levey et al. 202025 and FinnGen23) showed significant pairwise genetic correlations, ranging from rg=0.77 to rg=0.95 (Supplementary Table S4 and Figure S6), thus supporting that the GWAS results could be combined in a meta-analysis. We note that the SNP-heritability estimate37 for the iPSYCH cohort (hSNP2=0.167, SE=0.014, prevalence=0.2) was significantly higher (range of hSNP2 difference: 0.057 - 0.098) compared to the other cohorts (Supplementary Table S3 and Figure S7). This may reflect that the sample from the iPSYCH cohort is more homogeneous and includes a relatively young population, with early onset and severe cases of depression who have been treated in hospitals38.
