Integration of polygenic risk with single cell methylation data using met-scDRS.

met-scDRS effectively integrates single cell methylomes with GWAS data, revealing cell-type-specific epigenetic links to psychiatric disease risk at single-cell resolution.

• Why it matters: Understanding how genetic risk variants influence psychiatric traits through epigenetic mechanisms remains limited, hindering insights into disease pathology and potential interventions.
• What they did: The authors developed met-scDRS, a method that combines single cell methylation data with GWAS-identified disease genes, and applied it to a human brain dataset across 75 traits, generating disease relevance scores for individual cells.
• The result: The approach demonstrated high calibration and power, identified cell-type and spatial heterogeneity in psychiatric risk, and linked methylation patterns to pathways like synaptic formation, enabling refined understanding of disease mechanisms.