To measure heritability enrichment of eight brain disorder GWAS in active genomic regions in each cell/tissue-type, we used S-LDSC6 with chromHMM-defined chromatin states5. Since chromatin profiling hasn’t been performed in all cell/tissue-types (e.g. DNase hypersensitivity was missing for fetal brains, while H3K27ac ChIP-seq was not performed in the adult DLPFC), we instead used genomic regions that are active in each cell/tissue type using chromatin states defined by chromHMM59. We defined active genomic elements by the regions marked as Active transcription start sites (TSS, state 1), Flanking active TSS (state 2), Genic enhancers (state 6), and Enhancers (state 7), and repressive genomic elements marked as Heterochromatin (state 9), Repressed polycomb (state 13), Weak repressed polybcomb (state 14), and Quiescent (state 15) in the core 15-state model (https://egg2.wustl.edu/roadmap/web_portal/chr_state_learning.html). To further assess developmental stage specific heritability enrichment in the human brain tissue, we defined fetal active elements (elements that are active in the fetal brain and become repressive in the adult brain) and adult active elements (elements that are repressive in the fetal brain then become active in the adult brain). The SNP
