In this study, we used the LIBD RNA-seq, SNP genotype and whole-genome bisulfite sequencing (WGBS) datasets to evaluate differences in genetic ancestry in gene expression in the human brain (Fig. 1). We identified transcriptional features associated with genetic ancestry (African or European) in admixed neurotypical BA donors (n = 151). We quantified the contributions of common genetic variations to differences in genetic ancestry using a total of 425 samples, including the caudate nucleus (n = 122), dentate gyrus (n = 47), DLPFC (n = 123) and hippocampus (n = 133). Additionally, we examined the influence of genetic ancestry on DNA methylation using WGBS data of the admixed BA donors from the caudate nucleus (n = 89), DLPFC (n = 69) and hippocampus (n = 69). To confirm the genetic ancestry-associated differences in gene expression, we further examined transcriptional and DNA methylation differences in individuals of limited admixture (BAs ≥ 0.8 AA and white Americans (WAs) > 0.99 EA).