Zheng Xiaofei, Zhou Xin, Tong Li, Gu Wang, Wang Siyu, Yuang Wenkang, Zhang Chong, Zhang Chaoyang, Zhang Chao, Wan Bangbei
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China.
PLoS One. 2023 Sep 28;18(9):e0291086. doi: 10.1371/journal.pone.0291086. eCollection 2023.
This study systematically investigated the causal relationship between gastroesophageal reflux disease (GERD) and major depression (MD). Single-nucleotide polymorphisms (SNPs) associated with disorders of interest were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for GERD and MD were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. An available website tool (https://shiny.cnsgenomics.com/mRnd/) was used to calculate the statistical power of MR analysis. Meta-analysis was applied to test MD's average genetically predicted effect on GERD. Our MR study showed a bidirectional causal association between MD and GERD. Regarding MD to GERD, there was a positive association between them; the ORs were 1.500 (95% CI = 1.320-1.704; P = 4.91E-10) and 2.058 (95% CI = 1.868-2.267; P = 2.20E-48) in the IVW method, respectively. In addition, the meta-analysis also showed a strong positive causal association between MD and GERD. When exposure and outcome were reversed, genetic predisposition to GERD was significantly associated with the overall Risk of advanced MD (ieu-a-1187, OR = 1.982, 95% CI = 1.694-2.319, P = 1.41E-17; ieu-b-102, OR = 1.612, 95% CI = 1.530-2.700, P = 1.15E-70). Our study provides 100% power to detect the causal effect of MD on GERD and vice versa. Genetically predicted MD was positively associated with higher GERD risk, and vice versa. Our study reminds clinicians to pay attention to screening for GERD when diagnosing and treating MD and vice versa. Moreover, there may be positive feedback between MD and GERD when treating and preventing one disorder may benefit the treatment and prevention of the other.
本研究系统地调查了胃食管反流病（GERD）与重度抑郁症（MD）之间的因果关系。通过对欧洲血统个体进行全基因组关联研究（GWAS），筛选出与感兴趣疾病相关的单核苷酸多态性（SNP）。从英国生物银行提取GERD和MD的汇总水平数据。采用逆方差加权（IVW）方法作为主要分析方法。使用MR-Egger方法、最大似然法、MR-多效性残差和离群值（MR-PRESSO）方法以及MR-稳健调整轮廓评分（MR-RAPS）方法进行敏感性分析。还进行了MR-Egger回归、异质性检验、多效性检验和留一法检验以分析敏感性。使用MR Steiger检验来验证暴露与结局的方向性。使用一个可用的网站工具（https://shiny.cnsgenomics.com/mRnd/）来计算MR分析的统计功效。应用荟萃分析来检验MD对GERD的平均遗传预测效应。我们的MR研究显示MD与GERD之间存在双向因果关联。关于MD对GERD的影响，两者之间存在正相关；在IVW方法中，比值比（OR）分别为1.500（95%置信区间 = 1.320 - 1.704；P = 4.91E - 10）和2.058（95%置信区间 = 1.868 - 2.267；P = 2.20E - 48）。此外，荟萃分析也显示MD与GERD之间存在强正因果关联。当暴露和结局颠倒时，GERD的遗传易感性与晚期MD的总体风险显著相关（ieu-a-1187，OR = 1.982，95%置信区间 = 1.694 - 2.319，P = 1.41E - 17；ieu-b-102，OR = 1.612，95%置信区间 = 1.530 - 2.700，P = 1.15E - 70）。我们的研究有100%的功效检测MD对GERD的因果效应，反之亦然。遗传预测的MD与较高的GERD风险呈正相关，反之亦然。我们的研究提醒临床医生在诊断和治疗MD时要注意筛查GERD，反之亦然。此外，在治疗和预防一种疾病时，MD和GERD之间可能存在正反馈，这可能有利于另一种疾病的治疗和预防。
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