In order to construct the genome-wide S-LDSC matrix, and estimate stratified genetic covariance, we utilized pre-computed annotation files provided by the original S-LDSC authors32. In line with recommendations, we utilized all annotations from the most recent 1000 Genomes Phase 3 BaselineLD Version 2.257 that includes a total of 97 annotations ranging from coding, UTR, promoter, and flanking window annotations. For tissue specific histone marks, we included annotations constructed based on data from the Roadmap Epigenetics Project58 for narrowly defined peaks for DNase hypersensitivity, H3K27ac, H3K4me1, H3K4me3, H3K9ac, and H3K36me3 chromatin. For tissue-specific gene expression, we include annotations constructed based on RNA sequencing data from human tissues from Genotype-Tissue Expression (GTEx)59 and for annotations constructed from human, mouse, and rat microarray experiments from the Franke Lab (i.e., DEPICT)60. For both tissue-specific histone/chromatin marks and gene expression, we utilized only brain and endocrine relevant regions in addition to 5 randomly selected control regions from each (i.e., 10 controls total).
