Interpreting non-coding disease-associated human variants using single-cell epigenomics

Genome-wide association studies (GWAS) have linked hundreds of thousands of sequence variants in the human genome to common traits and diseases. However, translating this knowledge into a mechanistic understanding of disease-relevant biology remains challenging, largely because such variants are predominantly in non-protein-coding sequences that still lack functional annotation at cell-type resolution. Recent advances in single-cell epigenomics assays have enabled the generation of cell type-, subtype- and state-resolved maps of the epigenome in heterogeneous human tissues. These maps have facilitated cell type-specific annotation of candidate cis-regulatory elements and their gene targets in the human genome, enhancing our ability to interpret the genetic basis of common traits and diseases.