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

• Published in: Nature reviews. Genetics Vol. 24; no. 8; pp. 516 - 534
• Main Authors: Gaulton, Kyle J., Preissl, Sebastian, Ren, Bing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2023; Nature Publishing Group
• Subjects: 631/114/2785; 631/208; 631/208/177; 631/208/200; 631/337/572/2102; Agriculture; Animal Genetics and Genomics; Annotations; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cells; Disease; Epigenetics; Epigenomics; Gene expression; Gene Function; Gene mapping; Genetics; Genome, Human; Genome-wide association studies; Genome-Wide Association Study; Genomes; Human Genetics; Humans; Medical research; Medicine; Nucleotide sequence; Phenotype; Polymorphism, Single Nucleotide; Regulatory sequences; Regulatory Sequences, Nucleic Acid; Review Article; Transcription factors
• ISSN: 1471-0056; 1471-0064; 1471-0064
• DOI: 10.1038/s41576-023-00598-6

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.
In this Review, Gaulton et al. discuss how single-cell epigenomic methods generate cell type-, subtype- and state-resolved maps of candidate
cis
-regulatory elements in heterogeneous human tissues that can help to interpret the genetic basis of common traits and diseases.