Linkage disequilibrium (LD) score regression25 was performed to estimate the heritability explained by common SNPs (h2g) in the European-ancestry meta-analysis of case-control and family-based cohorts. The inclusion of related subjects may affect the LD score regression results due to the residual effect of family structure on the summary association data. To limit this potential confounder, the analyses was limited to variants assessed in more than 80% of the total sample and considering the effective sample size adjusted for both case-control ratio and family structure. The heritability analysis was not conducted on African-specific and trans-ancestry meta-analyses, because LD score regression is not suitable when analyzing GWAS summary data derived from admixed populations25. LD score regression analysis was performed considering HapMap3 SNPs26 and LD scores computed from the 1000 Genomes Project reference for European populations. Conversion of h2g estimates from observed scale to liability scale was performed accounting for the difference between population prevalence (ODexposed=1%, ODunexposed=1%, and OEcontrols=5%) and sample prevalence (ODexposed=55%, ODunexposed=22%, and OEcontrols=12%).
