Brain-region-specific enhancer maps link cell-type regulatory variation to neurological disease risk

Researchers have posted a preprint on bioRxiv presenting a large-scale epigenomic resource mapping transcriptional enhancer activity across neurons and glia from six distinct brain regions, each profiled in triplicate using H3K27ac ChIP-seq on cell populations sorted from post-mortem human tissue. The dataset was integrated with existing single-cell chromatin-accessibility data to interrogate which cell types and brain regions are most relevant to genetic risk for a range of neurological conditions.

Genetic variants associated with neurological traits have long been known to be enriched in active regulatory elements, but the diversity of neuronal and glial subtypes across brain regions has made it difficult to attribute risk variants to specific cell populations. The study finds that cell-type and brain-region specificity of enhancer activity meaningfully refines which variants are likely to affect which cells, offering new hypotheses about sites of disease pathology.

The resource complements existing single-cell transcriptomic and chromatin atlases of the human brain. Researchers studying the non-coding genome, gene regulation in neurological conditions, or functional annotation of GWAS loci are likely to find it particularly useful. This is a preprint and has not yet been peer-reviewed.