Unraveling the causal association between inflammatory bowel diseases and uveitis through mendelian randomization analysis

Abstract

Abstract To investigate the causal relationship between inflammatory bowel disease (IBD) and uveitis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis utilizing summary data from genome-wide association studies (GWAS). The primary statistical analysis was performed using the inverse-variance weighted (IVW) method. False discovery rate (FDR) correction was used to control for false positives in multiple testing. In addition, sensitivity analyses were carried out using the MR Egger intercept test and Cochran’s Q test. The MR analysis revealed that genetically determined IBD (OR = 1.141, 95% CI 1.080–1.205, P = 2.21 × 10−6, PFDR = 6.90 × 10−6), ulcerative colitis (UC) (OR = 1.113, 95% CI 1.032–1.201, P = 0.006, PFDR = 0.009), and Crohn’s diseases (CD) (OR = 1.073, 95% CI 1.017–1.133, P = 0.010, PFDR = 0.011) had a causal effect on uveitis. Conversely, the reverse MR analysis did not reveal significant causal link of uveitis on IBD, including its two subtypes. Furthermore, the results of the MR-Egger and weighted median methods were consistent with the IVW method. No evidence of heterogeneity or pleiotropy was detected by sensitivity analysis. Our findings confirm that IBD and its main subtypes had a causal connection with uveitis. Further research is needed to elucidate the underlying pathophysiological mechanisms driving this association.