Given the primary enrichment signal for immune-related pathways and cell types, we next investigated if immune variation was driving the observed transcriptional changes. Initially, we examined the enrichment of ancestry-associated DEGs for the major histocompatibility complex (MHC) region. We found global ancestry-associated DEGs of the caudate nucleus, DLPFC and hippocampus enriched for human leukocyte antigen (HLA) class II, while the dentate gyrus was enriched for Zinc-finger proteins associated with the extended MHC class I region (Fisher’s exact test, FDR < 0.05; Supplementary Fig. 15). While we found limited enrichment of local ancestry-associated DEGs for gene clusters of the MHC region across brain regions, we still observed significant enrichment of HLA class II genes for the caudate nucleus similar to global ancestry DEGs (Fisher’s exact test, FDR < 0.05; Supplementary Fig. 16).
