Post-transcriptional regulation via alternative polyadenylation and piRNA shapes macrophage responses in psoriasis.

Integrating multi-tissue genetic validations across GTEx, eQTLGen, and FinnGen datasets, we identified TDRKH as a robust psoriasis susceptibility gene (PPH4 > 0.92).

Single-cell RNA sequencing of psoriatic skin (4 patients, 17,734 cells) identified 17 cell types and 10 macrophage/myeloid subpopulations using marker gene-based annotation with TDRKH excluded from feature selection.

TDRKH expression was highest in IL-23-producing macrophages (IL23A+IL1B+), which were selectively enriched in lesional tissue.