Abstract
Crohn's disease (CD) is a chronic inflammatory disorder with potential progression to stricturing (B2) or penetrating (B3) phenotypes, leading to significant complications. Early identification of patients at risk for these complications is critical for personalized management. This study aimed to develop a predictive model using clinical data and a Korean-specific transcriptome-wide association study (TWAS) to forecast early progression in CD patients. A retrospective analysis of 430 Korean CD patients from 15 hospitals was conducted. Genotyping was performed using the Korea Biobank Array, and gene expression predictions were derived from a TWAS model based on terminal ileum data. Logistic regression models incorporating clinical and gene expression data predicted progression to B2 or B3 within 24 months of diagnosis. Among the cohort, 13.9% (60 patients) progressed to B2 and 16.9% (73 patients) to B3. The combined model achieved mean area under the curve (AUC) values of 0.788 for B2 and 0.785 for B3 progression. Key predictive genes for B2 included CCDC154, FAM189A2, and TAS2R19, while PUS7, CCDC146, and MLXIP were linked to B3 progression. This integrative model provides a robust approach for identifying high-risk CD patients, potentially enabling early, targeted interventions to reduce disease progression and associated complications.