be due to the overlap between functional regions (e.g. functional annotations for slightly different brain regions) when incorporating too many annotation tracks into the model, which will cause numerically unstable heritability estimates. This is because annotation-stratified LD score regression, the method we used to empirically estimate the informative prior for SNPs’ effect sizes, is a multiple linear regression model that regresses SNP-level summary statistics against annotation-stratified LD scores. When two functional annotation tracks are similar, the corresponding LD scores will also be correlated by definition. It is well understood that if multi-collinearity (i.e. correlation among covariates) in multiple regression leads to numerically unstable estimates for regression coefficients [30] (the heritability parameters in our case).
