Association between Cholelithiasis and Anxiety Disorder Based on the “Dan Zhu Jueduan”—A Two-Sample Mendelian Randomization Study

目的：基于“胆主决断”的中医理论，采用两样本孟德尔随机化方法探讨胆石症与焦虑症间的因果关系。方法：汇总数据来源于全基因组关联研究，暴露因素为胆石症，结局变量为焦虑症；孟德尔随机化分析通过逆方差加权法(inverse-variance weighted, IVW)、MR-Egger、加权中位数法(weighted median, WM)、简单模型法(simple mode)和加权模型法(weighted mode)实现；敏感性分析包括异质性检验、多效性检验和逐个剔除检验。结果：共筛选47个单核苷酸多态性。逆方差加权法结果显示，胆石症会增加焦虑症发生风险(OR = 1.0008, 95%CI: 1.0001~1.001, P Objective: Based on the traditional Chinese medicine theory of “Dan Zhu Jueduan”, the causal relationship between cholelithiasis and anxiety disorder was investigated by using two-sample Mendelian randomization (MR) method. Methods: Large-scale data were derived from genome-wide association studies (GWAS) with cholelithiasis as exposure factor and anxiety disorder as outcome variable. The inverse variance weighting (IVW), MR-Egger, weighted median (WME), simple mode (SM) and weighted mode (WM) were used to analyze the results, with the Inverse variance weighted method the main analysis method. And assess the reliability of the results for heterogeneity, pleiotropy, and sensitivity. Results: A total of 47 single nucleotide polymorphisms (SNPs) were selected. The Inverse variance weighted method showed that chololithiasis increased the risk of anxiety disorder (OR = 1.0008, 95%CI: 1.0001~1.001, P < 0.05). Multiple sensitivity analysis indicated that there was no pleiotropy and heterogeneity in the results of MR analysis, which verified the stability of the results. Conclusion: There is a positive causal relationship between cholelithiasis and anxiety disorder, which enriches the theoretical connotation of “Dan Zhu Jueduan” from the genetic perspective and lays a foundation for further research.