【摘要】 目的 运用孟德尔随机化(MR)分析方法，深入探究负性情绪相关心理因素(焦虑症、抑郁症、神经质)与胃食管反流病之间的因果关联。方法 从布里斯托大学IEU open GWAS数据库中提取上述3种负性情绪相关心理因素及胃食管反流病相关的全基因组关联研究(GWAS)数据。采用逆方差加权(IVW)法作为核心方法，并辅以MR-Egger法、加权中位数法(WME)进行结果验证与补充。进一步开展敏感性分析，运用Cochran’s Q检验评估异质性，通过MR-Egger截距检验水平多效性，同时采用“留一法”检验结果的稳健性。结果 经正向MR分析，IVW法显示焦虑症、抑郁症、神经质3种负性情绪相关心理因素均可增加胃食管反流病的发病风险(P<0.05);经反向MR分析，IVW法显示胃食管反流病亦可增加焦虑症、抑郁症的发病风险(P<0.001),同时可增加神经质人格相关的情绪不稳定性表现强度(P<0.001)。正、反MR分析，均未发现水平多效性，“留一法”分析均未发现对因果关系存在较大影响的单一IVs,证明了MR分析结果的稳健性。结论 负性情绪相关心理因素(焦虑症、抑郁症、神经质)与胃食管反流病的遗传易感性之间存在双向关联。更多还原

【Abstract】 Objective To explore the causal relationship between negative emotion-related psychological factors(anxiety disorder, depression, neuroticism) and gastroesophageal reflux disease(GERD) using Mendelian randomization(MR) analysis. Methods Genome-wide association study(GWAS) data related to the three negative emotion-related psychological factors and GERD were precisely extracted from the University of Bristol IEU open GWAS database. The inverse variance weighted(IVW) method was mainly used as the core method, supplemented by the MR-Egger method and the weighted median(WME) method for result verification and supplementation. Further sensitivity analysis was conducted, with Cochran’s Q test to assess heterogeneity, MR-Egger intercept test to evaluate horizontal pleiotropy, and the “leave-one-out” method to test the robustness of the results. Results Forward MR analysis by IVW method showed that three negative emotional psychological factors, namely anxiety disorder, depression, and neuroticism, could all increase the risk of developing GERD(P<0.05). Reverse MR analysis by IVW method indicated that GERD could also increase the risk of anxiety disorder and depression(P<0.001), and simultaneously enhance the intensity of emotional instability related to neurotic personality(P<0.001). Neither forward nor reverse MR analysis found horizontal pleiotropy, and “leave-one-out” analysis did not identify any single IVs that had a significant impact on the causal relationship, which confirmed the robustness of the MR analysis results. Conclusion There is a bidirectional association between negative emotion-related psychological factors(anxiety disorder, depression, neuroticism) and the genetic susceptibility of GERD.更多还原