Abstract
BACKGROUND: The elevated prevalence of venous thromboembolism (VTE) among individuals diagnosed with inflammatory bowel disease (IBD) necessitates thorough investigation. Analyzing the genetic association mechanisms between these conditions is essential for comprehending their concurrent manifestation. METHODS: Using genome-wide association study (GWAS) datasets for IBD and VTE, we applied a comprehensive approach to explore the genetic connections between these two diseases. The analysis was conducted in four steps: first, we assessed the overall genetic correlation between IBD and VTE using linkage disequilibrium score regression and genetic covariance analysis; next, we analyzed specific chromosomal regions to understand the genetic characteristics in these areas; then, we used the conditional/conjunctional false discovery rate (cond/conjFDR) method to better identify and quantify the shared genetic loci that contribute to both diseases' development. RESULTS: The genome-wide analysis revealed a strong genetic correlation between IBD, especially ulcerative colitis (UC), and VTE, while the correlation between Crohn's disease (CD) and VTE was weaker. A detailed regional analysis identified specific chromosomal areas with genetic links to both diseases. Using the conjFDR method, we confirmed the shared genetic components between these conditions and identified key genetic variants that influence the development of both diseases. CONCLUSION: This study provides genetic-level statistical evidence into the comorbidity mechanisms of IBD and VTE from a genetic standpoint, thereby enhancing the understanding of the underlying genetic basis contributing to their concurrent occurrence.