Predictive Performance and Clinical Application of PRS-15 for Venous Thromboembolism Risk in Chinese Orthopedic Patients: A Multicenter Prospective Case-Control Study

Background Venous Thromboembolism (VTE) is influenced by clinical and genetic factors. The Caprini score is widely used but does not account for population-specific genetic susceptibility in Chinese individuals. We previously developed a Chinese-specific 15-variant polygenic risk score (PRS-15) for VTE; however, its clinical performance and added value when combined with the Caprini score remain unclear. Methods We conducted a multicenter prospective case–control study at 18 hospitals in China (February 2023–March 2025), enrolling 1,013 postoperative VTE cases and 1,025 controls. Blood samples were genotyped for PRS-15, and clinical variables and outcomes were analyzed. Discrimination and calibration were assessed using AUC and the Hosmer–Lemeshow test. Two integrated models were constructed: Model 1, PRS-15T (tertiles: high/intermediate/low) plus Caprini; and Model 2, PRS-15B (binary: high/low) plus Caprini. K-means clustering identified optimal PRS-15 thresholds and integration strategies. Model performance was evaluated by sensitivity, specificity, and net reclassification improvement (NRI), with internal validation by bootstrap resampling. Results The PRS-15 model achieved an AUC of 0.702 (95% CI, 0.680–0.725; P < 0.001). For ternary classification (PRS-15T), the optimal thresholds were 2.230 and 1.730, while the optimal threshold for binary classification (PRS-15B) was 2.335. The sensitivities of Model 1 and Model 2 were 93.88% and 90.52%, respectively, both exceeding that of the Caprini score alone (87.36%). Model 2 demonstrated the highest specificity (33.85%), outperforming Model 1 (26.73%) and the Caprini score (21.37%), and achieved an NRI of 15.65%. Conclusion PRS-15 accurately discriminated VTE cases from controls and remained robust across age and sex subgroups. Adding PRS-15 to the Caprini score significantly improved risk assessment accuracy, supporting its clinical use for VTE risk evaluation in Chinese orthopedic surgical patients.