For REML analysis, we used a combination of the IOCDF-GC and OCGAS European datasets plus the cases from the IOCDF-GC and OCGAS trio dataset and performed an additional PCA analysis on this combined sample to remove any outliers. Genetic relationship matrices (GRM) for autosomes and chromosome X were generated for combined and sex-stratified datasets, removing any individuals who are closely related (IBD>0.05). All pruned imputed SNPs were used to determine the top 20 principal components using smartpca in EIGENSOFT (Price et al. 2006). Genomic-relatedness-based restricted maximum-likelihood (GREML) analysis was performed on the autosomes and the X chromosome (taking into account dosage compensation, Supplementary Methods) using GRMs and the top 20 ancestry covariates. The same range of prevalence estimates, as in the LDSC analysis, were used to transform heritability to the liability scale. Bivariate GREML analysis was performed to assess the genetic correlation between the sexes. To determine the proportion of the total heritability contributed by each chromosome (including the X chromosome), a separate GRM was generated for each of the 23 chromosomes. Then, all chromosomes were analyzed jointly in a single GREML analysis with 20 PCs to account for population substructure.
