抑郁症与胃食管反流病的双向孟德尔随机化研究

Psychosocial Disorders and Gastroesophageal Reflux Disease: A Bidirectional Mendelian Randomization Study

摘要: 目的：观察性研究揭示了抑郁症与胃食管反流病(Gastroesophageal reflux disease, GERD)之间的双向联系。然而，无论是方向还是因果关系都不清楚。这项孟德尔随机化(Mendelian randomization, MR)研究旨探究抑郁症和胃食管反流病之间的因果关系。方法：从基因组关联研究数据库(Genome-wide association study, GWAS)中提取符合条件的数据集。运用逆方差加权法(IVW)、加权中值法、加权模式法、简单模式法及MR-Egger法进行两样本孟德尔随机化(Two-sample Mendelian randomization, TSMR)分析。使用“留一法”(leave-one-out)、MR-PRESO和漏斗图用于评估异质性和水平多向性的证据。结果：遗传决定的抑郁症[IVW OR = 1.343; 95% CI: 1.175, 1.524; P = 6.449 × 10−7]与胃食管反流病的风险相关。反向分析结果显示胃食管反流病对抑郁症的因果效应较小，但有统计学意义[IVW OR = 1.021; 95% CI: 1.017, 1.025; P = 9.47 × 10−24]。同时。在亚型分析中，抑郁症与巴雷特食管相关[IVW OR = 1.823; 95% CI 1.517, 2.142; P = 0.014]。结论：本孟德尔随机化研究表明抑郁症与胃食管反流病之间存在双向因果关系。

Abstract: Objective: Observational studies have revealed a bidirectional association between depression and gastroesophageal reflux disease (GERD). However, neither the direction nor the causal chain is clear. The bidirectional causality between depression and GERD is intended to be examined by this Men-delian Randomization (MR) study. Methods: The eligible datasets were extracted from the data-bases from the Genome-Wide Association Studies (GWAS). Along with Inverse-variance weighted (IVW), the other MR methods involved were weighted median, weighted mode, simple mode, and MR-Egger. Diagnostic leave-one-out, MR-PRESSO and funnel-plot were performed to evaluate for evidence of heterogeneity and horizontal pleiotropy. Results: Genetically determined depression [IVW odds ratio (OR) = 1.343; 95% CI 1.175, 1.524; P = 6.449 × 10−7] were associated with the risk of GERD. The results of reverse MR analysis indicated a statistically significant but small causal ef-fect of GERD on depression [IVW OR = 1.021; 95% CI 1.017, 1.025; P = 9.47 × 10−24]. Meanwhile, in subtype analyses depression was suggestively associated with Barrett’s esophagus (BE) [IVW OR = 1.823; 95% CI 1.517; 2.142; P = 0.014]. Conclusions: This study supports a bidirectional causal re-lationship between depression and gastroesophageal reflux disease.