基于“胆主决断”探讨胆石症和焦虑症的关联性——一项两样本孟德尔随机化研究

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

摘要: 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 < 0.05)。多项敏感性分析提示孟德尔随机化分析结果不存在多效性和异质性，验证了研究结果的稳定性。结论：胆石症与焦虑症之间存在正向的因果关系，从遗传角度丰富了“胆主决断”理论内涵，亦为进一步深入研究奠定了基础。

Abstract: 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.