significant depletion of DEGs (global and local) for neuronal cell types. Moreover, we observed immune-related pathways and associated cell types (that is, microglia and perivascular macrophages) for DEGs upregulated with increasing AA proportion in the caudate nucleus and upregulated with increasing EA proportion in the dentate gyrus, DLPFC and hippocampus. Although we found some differences in glial cell subtypes25 (analysis of variance (ANOVA), FDR < 0.05; Supplementary Fig. 14) using publicly available single-cell data from brain regions with similar compositions26, no specific glial subtype25 showed directionality of the ancestry effect (Supplementary Fig. 12). Altogether, these results suggest that ancestry-associated DEGs in the human brain are strongly associated with a brain-specific immune response, with the direction of effects varying according to brain region.
