The causal impact of genetically predicted inflammatory bowel disease on extraintestinal manifestations: a mendelian randomization study

Our findings indicated that genetically predicted IBD had a robust causal relationship with an increased risk of specific conditions, including EN (OR, 1.20; 95% CI, 1.09-1.32; p < 0.01), uveitis (OR, 1.15; 95% CI, 1.11-1.20; p < 0.01), PSC (OR, 1.21; 95% CI, 1.13-1.28; p < 0.01), and spondyloarthritis (OR, 1.19; 95% CI, 1.14-1.23; p < 0.01). In subgroup analyses, the causal effects of both UC and CD on EN, uveitis, PSC, and spondyloarthritis were also significant and robust. Additionally, no significant evidence of causality was observed between genetically predicted IBD, UC, and CD, and the occurrence of both episcleritis and scleritis. The results of reverse causality analysis indicated a robust causal association between genetically predicted PSC and the elevated risk of IBD (OR, 1.21; 95% CI, 1.15-1.29; p < 0.01), UC (OR, 1.27; 95% CI, 1.17-1.37; p < 0.01), and CD (OR, 1.10; 95% CI, 1.02-1.20; p < 0.01). Additionally, spondyloarthritis had a causal relationship with an increased risk of both IBD (OR, 1.03; 95% CI, 1.01-1.06; p < 0.01) and UC (OR, 1.05; 95% CI, 1.02-1.08; p < 0.01).