Multi-cytokine based TWAS for seven inflammatory skin disorders identify candidate causal genes in keratinocytes - PubMed
2 hours ago
- #TWAS
- #inflammatory skin disorders
- #keratinocytes
- TWAS across multiple pro-inflammatory cytokine stimulations in keratinocytes identified 274 loci with significant gene associations for seven inflammatory skin diseases.
- Notable genes implicated include ERAP2 for psoriasis under IL-17A+TNF stimulation, WNT10A for acne with IFNγ, and RAET1L, MAP3K11, and ITGAM for alopecia areata, acne, and SLE with TNF.
- High colocalization with GWAS signals (p = 1.03×10-15) demonstrated the method's effectiveness, capturing over 85% of genes with colocalizing eQTLs.
- Spatial profiling confirmed that TWAS signals in keratinocytes are influenced by nearby TNF/IL-17 expressing cells in psoriatic skin, highlighting the interplay between genetics and local cellular environment.
- The study concludes that modeling gene expression across cellular states enhances TWAS power and provides insights into how susceptibility loci modulate cytokine responses in keratinocytes.