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

Nat Rev Genet. 2023 Aug;24(8):516-534. doi: 10.1038/s41576-023-00598-6. Epub 2023 May 9.

Abstract

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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epigenomics*
  • Genome, Human
  • Genome-Wide Association Study*
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Regulatory Sequences, Nucleic Acid