PDF(Pubmed)
Abstract：
OBJECTIVE: This study aimed to use Mendelian randomization (MR) to investigate the potential causal association between inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH).
METHODS: Two-sample MR was performed to estimate the causal effect of IBD on AIH. The primary analysis employed the inverse variance weighted (IVW) method in univariable MR analysis, supplemented by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. The p values were adjusted by FDR p-value adjustment. In the replication analysis, the primary IVW analysis was repeated and then pooled by meta-analysis. Sensitivity analyses were performed using Cochran\'s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out, and funnel plot analysis to evaluate the robustness of the MR findings. Additionally, multivariable MR (MVMR) was employed to estimate the direct causal effect of IBD on the risk of AIH.
RESULTS: In univariable MR analysis, a significant positive causal association was observed between IBD (both Crohn\'s disease (CD) or ulcerative colitis (UC)) and the risk of AIH (for CD and AIH, the IVW odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.00-1.16, P = 0.045, FDR P = 0.045; for UC and AIH, the IVW OR = 1.07, 95% CI = 1.00-1.13, P = 0.038, FDR P = 0.076). Furthermore, no significant positive correlation between IBD and the risk of AIH (OR = 1.13, 95% CI = 0.94-1.35, P = 0.194). Sensitivity analysis revealed no pleiotropic bias. MVMR analysis further confirmed the direct causal effect of CD or UC on the risk of AIH after adjusting for the common risk factors (cigarettes per day and osteoporosis). In the replication analysis, the positive causal association between UC and the risk of AIH remain significant (the IVW odds ratio (OR) = 1.32, 95% CI = 1.18-1.48, P = 2.90E-06). While no significant positive association was observed between CD or IBD and the risk of AIH in the replication analysis, a suggestive positive association between the identified risk factors (UC, CD, and IBD) and the risk of AIH was detected in the meta-analysis (OR = 1.09, 95% CI = 1.05-1.13, P<0.0001).
CONCLUSIONS: This MR study revealed a positive impact of the identified risk factors (CD, UC and IBD) on the risk of AIH within the European population.
METHODS: Two-sample MR was performed to estimate the causal effect of IBD on AIH. The primary analysis employed the inverse variance weighted (IVW) method in univariable MR analysis, supplemented by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. The p values were adjusted by FDR p-value adjustment. In the replication analysis, the primary IVW analysis was repeated and then pooled by meta-analysis. Sensitivity analyses were performed using Cochran\'s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out, and funnel plot analysis to evaluate the robustness of the MR findings. Additionally, multivariable MR (MVMR) was employed to estimate the direct causal effect of IBD on the risk of AIH.
RESULTS: In univariable MR analysis, a significant positive causal association was observed between IBD (both Crohn\'s disease (CD) or ulcerative colitis (UC)) and the risk of AIH (for CD and AIH, the IVW odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.00-1.16, P = 0.045, FDR P = 0.045; for UC and AIH, the IVW OR = 1.07, 95% CI = 1.00-1.13, P = 0.038, FDR P = 0.076). Furthermore, no significant positive correlation between IBD and the risk of AIH (OR = 1.13, 95% CI = 0.94-1.35, P = 0.194). Sensitivity analysis revealed no pleiotropic bias. MVMR analysis further confirmed the direct causal effect of CD or UC on the risk of AIH after adjusting for the common risk factors (cigarettes per day and osteoporosis). In the replication analysis, the positive causal association between UC and the risk of AIH remain significant (the IVW odds ratio (OR) = 1.32, 95% CI = 1.18-1.48, P = 2.90E-06). While no significant positive association was observed between CD or IBD and the risk of AIH in the replication analysis, a suggestive positive association between the identified risk factors (UC, CD, and IBD) and the risk of AIH was detected in the meta-analysis (OR = 1.09, 95% CI = 1.05-1.13, P<0.0001).
CONCLUSIONS: This MR study revealed a positive impact of the identified risk factors (CD, UC and IBD) on the risk of AIH within the European population.
摘要：
目的：本研究旨在利用孟德尔随机化（MR）研究炎症性肠病（IBD）与自身免疫性肝炎（AIH）之间的潜在因果关系。
方法：进行两个样本MR以评估IBD对AIH的因果影响。主要分析在单变量MR分析中采用逆方差加权(IVW)方法，补充了包括MR-Egger在内的其他方法，加权中位数，简单模式，和加权模式。通过FDRp值调整来调整p值。在复制分析中，重复进行主要IVW分析,然后进行荟萃分析.使用CochranQ检验进行敏感性分析，MR-Egger截距测试,MR-PRESSO,leave-one-out,和漏斗图分析，以评估MR检查结果的稳健性。此外,多变量MR（MVMR）用于评估IBD对AIH风险的直接因果关系。
结果：在单变量MR分析中，在IBD(克罗恩病(CD)或溃疡性结肠炎(UC))和AIH风险之间观察到显著的正相关(对于CD和AIH,IVW比值比（OR）=1.10，95％置信区间（CI）=1.00-1.16，P=0.045，FDRP=0.045；对于UC和AIH，IVWOR=1.07，95%CI=1.00-1.13，P=0.038，FDRP=0.076）。此外，IBD与AIH风险无显著正相关(OR=1.13,95%CI=0.94~1.35,P=0.194)。敏感性分析显示没有多效性偏差。MVMR分析进一步证实了CD或UC对AIH风险的直接因果效应在校正常见危险因素（每天吸烟和骨质疏松症）后。在复制分析中，UC与AIH风险之间的正因果关系仍然显著(IVW比值比(OR)=1.32,95%CI=1.18~1.48,P=2.90E-06).虽然在复制分析中没有观察到CD或IBD与AIH风险之间的显著正相关，已识别的危险因素(UC，CD,和IBD），并且在荟萃分析中检测到AIH的风险（OR=1.09，95％CI=1.05-1.13，P<0.0001）。
结论：这项MR研究揭示了已确定的风险因素的积极影响（CD，UC和IBD）对欧洲人群AIH的风险。
方法：进行两个样本MR以评估IBD对AIH的因果影响。主要分析在单变量MR分析中采用逆方差加权(IVW)方法，补充了包括MR-Egger在内的其他方法，加权中位数，简单模式，和加权模式。通过FDRp值调整来调整p值。在复制分析中，重复进行主要IVW分析,然后进行荟萃分析.使用CochranQ检验进行敏感性分析，MR-Egger截距测试,MR-PRESSO,leave-one-out,和漏斗图分析，以评估MR检查结果的稳健性。此外,多变量MR（MVMR）用于评估IBD对AIH风险的直接因果关系。
结果：在单变量MR分析中，在IBD(克罗恩病(CD)或溃疡性结肠炎(UC))和AIH风险之间观察到显著的正相关(对于CD和AIH,IVW比值比（OR）=1.10，95％置信区间（CI）=1.00-1.16，P=0.045，FDRP=0.045；对于UC和AIH，IVWOR=1.07，95%CI=1.00-1.13，P=0.038，FDRP=0.076）。此外，IBD与AIH风险无显著正相关(OR=1.13,95%CI=0.94~1.35,P=0.194)。敏感性分析显示没有多效性偏差。MVMR分析进一步证实了CD或UC对AIH风险的直接因果效应在校正常见危险因素（每天吸烟和骨质疏松症）后。在复制分析中，UC与AIH风险之间的正因果关系仍然显著(IVW比值比(OR)=1.32,95%CI=1.18~1.48,P=2.90E-06).虽然在复制分析中没有观察到CD或IBD与AIH风险之间的显著正相关，已识别的危险因素(UC，CD,和IBD），并且在荟萃分析中检测到AIH的风险（OR=1.09，95％CI=1.05-1.13，P<0.0001）。
结论：这项MR研究揭示了已确定的风险因素的积极影响（CD，UC和IBD）对欧洲人群AIH的风险。
