Furthermore, we observed enrichment for heritability of Alzheimer’s disease (AD) for ancestry-associated DEGs across the DLPFC, hippocampus and caudate nucleus accounting for 26%, 23% and 30% of total heritability, respectively (Supplementary Fig. 30). These enrichments were mainly driven by protein-coding DEGs associated with an increase in AA proportion for the DLPFC (enrichment fold = 2.0, FDR = 0.013; Fig. 6) and hippocampus (enrichment fold = 1.9, FDR = 0.02; Fig. 6). We found the opposite effect with an increase in EA proportion for the caudate nucleus when considering all DEGs (Supplementary Fig. 30), which disappeared when we considered only protein-coding DEGs (Fig. 6). Cell type enrichment analysis of astrocytes, however, showed ancestry-specific effects consistent with our finding for the caudate nucleus (increased EA proportion; Supplementary Fig. 10). Moreover, we found ancestry-associated glial cell subtypes (that is, microglia (MG0) and astrocytes (AST1 and AST7)) significantly enriched for AD heritability (enrichment fold > 2.2, FDR < 0.01; Supplementary Fig. 32) and ancestry-associated DEG enrichment for multiple activated microglia states36 (Supplementary Fig. 33a). These microglia states were associated with mouse AD-associated microglial genes and AD GWAS signals (Supplementary Fig. 33b), as well as late-response AD-related genes (Supplementary Fig. 34).
