炎症性肠病与20种感染性疾病关系的孟德尔随机化研究和中介效应分析OA

Objective To investigate the causal associations between inflammatory bowel disease(IBD)and 20 infectious diseases,and to analyze the mediating effects of glucocorticoids and immunosuppressants.Methods Based on genome-wide association study(GWAS)summary data,a bidirectional two-sample Mendelian randomization(MR)approach was employed to evaluate the causal effects between IBD,ulcerative colitis(UC),Crohn's disease(CD),and 20 infectious diseases.A two-step MR was utilized to assess the mediating effects of medications.The inverse-variance weighted(IVW)method was used as the primary analysis,complemented by MR-Egger,weighted median,and weighted mode methods for validation.Sensitivity analyses were performed using Cochran's Q test,MR-PRESSO,MR Steiger test,and leave-one-out analysis.The results were adjusted for multiple testing using the Benjamini-Hochberg procedure.Results After multiple testing correction,both IBD(OR=1.159,95％CI:1.092-1.230)and UC(OR=1.157,95％CI:1.093-1.225)were significantly associated with an increased risk of Clostridioides difficile infection(both FDR＜0.05).CD was associated with a higher risk of hepatitis C virus infection(OR=1.143,95％CI:1.052-1.241,FDR＜0.05).Furthermore,the two-step MR analysis revealed no significant mediating effects of glucocorticoids and immunosuppressants in these causal associations.Conclusion Significant causal associations exist between IBD and specific infectious diseases.This highlights the necessity for clinical vigilance regarding opportunistic infection risk management in patients with IBD,and warrants further investigation into the potential mechanisms of viral exposure in IBD pathogenesis.