Association of a Han Chinese urticaria-derived polygenic risk score with chronic spontaneous urticaria susceptibility and advanced systemic treatment use.

Abstract

Background: Chronic spontaneous urticaria (CSU) is a heterogeneous mast cell-driven disease with variable treatment needs, but the clinical relevance of Han Chinese urticaria-derived polygenic risk scores (PRSs) remains unclear.

Objective: To evaluate the associations between Han Chinese urticaria-derived PRSs, CSU susceptibility, and advanced systemic treatment use.

Methods: We conducted a retrospective case-control study using Taiwan Precision Medicine Initiative participants at Taichung Veterans General Hospital. CSU cases and matched controls were identified using diagnostic codes and electronic medical records. Five urticaria-derived PRS models were evaluated using receiver operating characteristic curves (ROC). The best-performing PRS was categorized into quartiles, and logistic regression assessed associations with CSU susceptibility and advanced systemic treatment use.

Results: The study included 4,676 patients with CSU and 18,704 matched controls. The Lassosum-based urticaria-derived PRS demonstrated the highest area under the ROC curve. Higher PRS quartiles were associated with increased CSU susceptibility, especially Q4. Among 4,550 patients with CSU and available PRS data, higher PRS quartiles were associated with advanced systemic treatment use, with sex-stratified differences observed.

Conclusions: A Han Chinese urticaria-derived PRS was associated with CSU susceptibility and advanced systemic treatment use, supporting its potential role as an adjunctive genetic risk-stratification marker in CSU.