To bridge this gap, we need studies of the biological impact of genetic variation on molecular traits (for example, mRNA and DNA methylation) in disease-relevant tissues of diverse populations. An obvious impediment to undertaking this task is the limited availability of brain tissue from AA individuals. Currently, the most widely used resource for human postmortem tissue is the Genotype-Tissue Expression Project (GTEx), which has RNA sequencing (RNA-seq) and single-nucleotide polymorphism (SNP) genotype data from 13 brain regions (114–209 individuals per region). However, most GTEx brain samples are of European genetic ancestry (EA); for some brain regions, GTEx has no individuals of non-EA. In comparison, the BrainSeq Consortium, a collaboration between seven pharmaceutical companies and the Lieber Institute for Brain Development (LIBD), includes 784 samples from Black Americans (BAs) across 587 unique individuals, with a mean age of 44. While reports from this consortium and other large-scale analyses in the brain—including from the hippocampus, caudate nucleus, dorsolateral prefrontal cortex (DLPFC) and granule cells of the dentate gyrus—have samples of diverse genetic ancestry10–16, they have typically been ‘adjusted’ for ancestry status, which limits our understanding of ancestry-specific effects in the brain.
