Chromatin accessibility provides a window into the genetic etiology of human brain disease.

Abstract

Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain. The integration of single-cell technologies with genome-wide association studies (GWAS) and transcriptomic data has further advanced our understanding of cell-specific chromatin dynamics. This review discusses recent findings regarding the role played by chromatin accessibility in brain disease, highlighting the need for high-quality data and rigorous computational tools. Future directions include spatial chromatin studies and CRISPR-based functional validation to bridge genetic discovery and clinical applications, paving the way for targeted gene-regulatory therapies.