孟德尔随机化分析原发硬化性胆管炎合并炎症性肠病与结直肠癌的关系OA

Objective To evaluate the bidirectional causal relationship between primary sclerosing cholangi-tis(PSC)complicated with inflammatory bowel disease(IBD)and colorectal cancer(CRC)using Mendelian randomization(MR).Methods Independent single nucleotide polymorphisms(SNPs)strongly associated with PSC complicated with IBD,PSC complicated with ulcerative colitis(UC),and PSC complicated with Crohn's disease(CD)were extracted as instrumental variables from genome-wide association study data according to preset thresholds.The inverse variance weighted(IVW)method was used to assess the associa-tion of the three exposures with the risk of CRC.Cochran Q test was applied to evaluate the heterogeneity of SNPs.MR-Egger intercept test was performed to detect the horizontal pleiotropy of SNPs.MR-PRESSO test was used to identify the presence of outlier SNPs.Leave-one-out sensitivity analysis was conducted to verify whether the MR results were affected by a single SNP.Steiger directionality test was used to examine reverse causality.Results Three SNPs were included for PSC-IBD and four SNPs for PSC-UC in the MR analy-sis.After relaxing certain criteria,only one SNP was included for PSC-CD.IVW analysis indicated a causal relationship between PSC-IBD,PSC-UC and CRC.Sensitivity analysis showed no heterogeneity among the included SNPs.MR-Egger test suggested no horizontal pleiotropy in the MR results.MR-PRESSO test detected no outlier SNP for PSC-UC,while MR-PRESSO analysis could not be performed for PSC-IBD due to insufficient instrumental variables.Leave-one-out sensitivity analysis showed that the causal estimates were not significantly affected by any single SNP.Steiger directionality test did not support reverse causality.Con-clusion Genetically predicted PSC complicated with IBD or UC is associated with an increased risk of CRC.However,only one SNP was available for PSC-CD,which precluded valid MR analysis.