重度抑郁症与胃溃疡之间的双向关联：孟德尔随机化研究

<b>抽象</b><b>重要性</b>大量新出现的证据表明度抑郁症 （MDD） 与胃溃疡 （GU） 之间存在关联。然而，尽管MDD和GUs之间开始了从属关系，但明确的因果相互作用和轨迹仍然处于模糊状态，因此MDD和GUs之间的反向相关性有待明确的解释。<b>目的</b>研究 MDD 和 GU 之间的双向关联，采用遗传知情方法来评估合理的因果推论。<b>设计、设置和参与者</b>双样本孟德尔随机化MR），这些患者来自芬兰 （finngen） 和综合流行病学单位 （IEU） 数据库。该研究还利用了关于被诊断患有MDD的个体（n = 807,553）的最大可用非重叠全基因组关联研究（GWAS）作为遗传工具。上述GWAS是在大量不同的观察队列中进行的，包括Finngen，IEU OpenGWAS项目，以及精神病学基因组学联盟（PGC）（特别是MDD）中的其他参与研究，重点是欧洲血统的成年人。随后使用逆方差加权 （IVW） 荟萃分析技术合成从每种遗传仪器获得的 MR 估计值。替代方法，包括但不限于加权中位数、MR Egger 和 MR-多效性残差和异常值 （PRESSO） 技术，也与各种灵敏度分析相结合，以仔细评估水平多效性并有效去除异常值。<b>结果</b>源自 IVW 方法的 MR 研究结果表明，MDD 显着增加了感染 GU [比值比 （OR） = 1.23,95% 置信区间 （CI） 1.08-1.41，P <i>P</i> = 2.33 × 10-3]。此外，其他方法（如加权中位数）的 MR 结果,，与 IVW 方法产生了一致的结果。此外，敏感性分析显示，结局是有弹性的，没有观察到多效性或异质性。相反，反向 MR 分析表明 GU 不会增加 MDD 风险的发生率。<b>结论</b>这项 MR 研究证实了 MDD 与 患 GU 风险升高之间存在重要联系。因此，在MDD患者的对症治疗中，应纳入相应的GU保护预防措施， 这 以规避GU的进展。

<b>Abstract</b><b>Importance</b>A growing body of emerging evidence indicates an association between major depressive disorder (MDD) and gastric ulcer (GU). However, despite the growing number of observed associations between MDD and GUs, definitive causal interactions and temporal trajectories remain unclear, and the bidirectional correlation between MDD and GUs requires definitive explanation.

<b>Objective</b>The objective of this study was to investigate the bidirectional association between MDD and GU, using genetically informed approaches to evaluate plausible causal inferences.

<b>Design, Setting, and Participants</b>This was a two-sample Mendelian randomization (MR) study using data from the FinnGen and Integrated Epidemiology Unit (IEU) databases. This study utilized the largest available non-overlapping genome-wide association study (GWAS) of individuals diagnosed with MDD (n = 807,553) as the genetic instrument. This GWAS was conducted across multiple diverse observational cohorts, including FinnGen, the IEU OpenGWAS Project, and other participating studies within the Psychiatric Genomics Consortium (PGC) focused specifically on MDD, with a sample of adults of European ancestry. Subsequently, inverse variance weighted (IVW) meta-analysis was employed to synthesize MR estimates derived from each genetic instrument. Alternative methods, including but not limited to weighted median, MR Egger, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) techniques, were combined with various sensitivity analyses to rigorously assess horizontal pleiotropy and effectively eliminate outliers.

<b>Results</b>MR results from the IVW method showed that MDD significantly increased the risk of GU [odds ratio (OR) = 1.23, 95% confidence interval (CI) 1.08–1.41, P = 2.33 × 10⁻³]. Additionally, MR results from other methods such as weighted median yielded consistent findings with the IVW approach. Sensitivity analyses demonstrated that the results were robust, with no observed pleiotropy or heterogeneity. Conversely, reverse MR analysis indicated that GU did not increase the incidence of MDD risk.

<b>Conclusions</b>This MR study confirmed a significant association between MDD and elevated risk of GU. Accordingly, corresponding protective preventive measures against GU should be included in the symptomatic treatment of patients with MDD to avoid the progression of GU.