Functional dissection of complex trait variants at single-nucleotide resolution - PubMed
3 hours ago
- #genetics
- #regulatory variants
- #disease risk
- Identified 13,121 regulatory variants with high precision using a massively parallel reporter assay in 5 diverse cell types.
- Found that 69% of regulatory variants can be explained by the disruption of a known transcription factor binding motif.
- Investigated mechanisms of 136 variants using saturation mutagenesis, assigning affected transcription factors for 91% of variants without a clear canonical mechanism.
- Detected regulatory epistasis at 11% of tested regulatory variants in close proximity.
- Identified multiple functional variants on the same haplotype at a subset of trait-associated loci.
- Provides insights into the regulatory grammar underlying disease risk.