The estimates of heritability from both univariate (Fig. 3a, red and pink bars) and bivariate (Fig. 3a, blue bars) analyses are more heterogeneous for bipolar disorder, major depressive disorder and ADHD than they are for schizophrenia and ASD. Several factors could explain why SNP-based heritabilities from univariate analyses of a single data set could generate higher estimates than bivariate analyses of independent data sets35, including loss of real signal or dilution of artifacts. Loss of real signal might occur because individual cohorts are more homogeneous, both phenotypically (for example, owing to use of the same assessment protocols) and genetically (for example, because LD between causal variants and analyzed SNPs might be higher within than between cohorts). Artifacts could also generate consistent differences in case genotypes relative to control genotypes within case-control data sets. In the derivation of our methodology18, we emphasized that any factors making SNP genotypes of cases more similar to those of other cases and making the genotypes of controls more similar to those of other controls would produce SNP-based heritability. The fitting as covariates of principal components
