Extended Data Fig. 7: Disease heritability enrichment in hGN promoter and enhancer regions.

a. Heritability enrichments (top) and p-values of heritability enrichment (bottom) of the 1G hGN H3K27ac promoter and enhancer regions across neurological and non-neurological disorders. b. p-values of heritability enrichment of 4G hGN H3K27ac promoter and enhancer regions across neurological and non-neurological disorders. c. Heritability enrichments (left) and p-values of heritability enrichment (right) of the inducible and constitutive H3K27ac enhancer regions across neurological diseases for both 4G (top) and 1G (bottom), showing significant enrichment for only constitutive enhancer regions. d. p-values of heritability enrichment of 4G (top) hGN inducible and constitutive enhancers (central 500 bp of 4G ATACseq peaks within 4G H3K27ac enhancer regions) across neurological disorders, and (bottom) 1G heritability enrichments (left) and p-values of heritability enrichment (right), showing significant enrichment for only constitutive enhancers. e. p-values of heritability enrichment of 4G (left) hGN inducible and constitutive promoters across neurological disorders, and 1G heritability enrichments (center) and p-values of heritability enrichment (right), showing significant ASD and BP heritability enrichment in inducible promoters but not constitutive promoters. f. Heritability enrichment (top) p-values of heritability enrichment (bottom) of the inducible and constitutive 1G (left) and 4G (right) H3K27ac promoter regions across neurological diseases. g. Proportions of each hGN scRNAseq cluster’s inducible gene list that have inducible promoters by 1G H3K27ac ChIPseq. Proportions are calculated at multiple gene expression fold-change cut-off thresholds. Cluster 10 (striatal spiny projection neuron-like cells) inducible genes have the highest proportion of SFARI ASD-associated genes, regardless of gene expression fold-change cut-off threshold. h. LDSC heritability enrichments were calculated using summary statistics from two schizophrenia (SCZ) GWASs: Psychiatric Genomics Consortium (PGC), 2014 and Pardiñas, et al., 2018. The latter incorporates 40.5 K cases compared to 37 K in the 2014 PGC study and uses fewer controls (63 K vs 113 K). i. LDSC heritability enrichment calculations were repeated for all neurological disorders in parallel with Alzheimer’s Disease (AD), using the summary statistics from Lambert, J., Ibrahim-Verbaas, C., Harold, D. et al., Nature Genetics, 2013. Please note that the GWASs for the other neurological disorders included in our analyses were uniformly processed by the PGC whereas the AD GWAS was processed differently, which may contribute to the relatively large error bars associated with the AD analysis. All LDSC Plots are color coded according to Fig. 6a. Each heritability enrichment value is provided in bar plot (+/- std. error). p-values of heritability enrichment are multi-test corrected and heritability enrichment bars with p = or > 0.05 are cross-hatched. Exact p-values are provided in Supplementary Data 14.