Causal Relationship Between Gastroesophageal Reflux Disease and the Risk of Chronic Rhinosinusitis: Insights from Multivariable and Mediation Mendelian Randomization Analysis.

Ce Wu, Zengxiao Zhang, Xudong Yan, Lin Wang, Longgang Yu, Yan Jiang
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Abstract

Background: Previous studies have shown an association between chronic rhinosinusitis (CRS) and gastroesophageal reflux disease (GERD). However, the findings of these studies are controversial, and evaluating this association could help in the treatment of CRS. Thus, we aimed to clarify the relationship between GERD and CRS. Methods: We conducted a Mendelian randomization (MR) study. Pooled data on CRS, GERD, and their associated risk factors were extracted from large genome-wide association studies. Independent single-nucleotide polymorphisms were rigorously screened as instrumental variables. Causal associations between GERD and CRS were assessed, and mediation analyses were performed using multivariate and 2-step MR. Asthma served as a mediator because of its association with both CRS and GERD. Sensitivity tests were also performed. Results: MR analysis showed that genetically predicted GERD was associated with an increased risk of CRS (P < .001). Multivariate MR analysis showed that the effect of GERD on CRS was relatively independent. Mediation analysis showed that asthma mediated the association with a mediation effect of 21.07% (95% CI, 2.70%-40.18%). Sensitivity analyses did not reveal any significant effects of pleiotropy and heterogeneity. Conclusions: We found a causal relationship between genetically predicted GERD and an increase in the risk of CRS. As a mediator, asthma contributed to the effect of GERD on CRS. This study provides high-quality causal evidence for the prevention of CRS.

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胃食管反流病与慢性鼻炎风险之间的因果关系:多变量和调解孟德尔随机分析的启示》。
背景:以往的研究表明,慢性鼻炎(CRS)与胃食管反流病(GERD)之间存在关联。然而,这些研究的结果存在争议,评估这种关联有助于治疗 CRS。因此,我们旨在阐明胃食管反流病与 CRS 之间的关系。研究方法我们进行了一项孟德尔随机化(MR)研究。从大型全基因组关联研究中提取了 CRS、胃食管反流病及其相关风险因素的汇总数据。作为工具变量,对独立的单核苷酸多态性进行了严格筛选。评估了胃食管反流病与 CRS 之间的因果关系,并使用多变量和两步 MR 进行了中介分析。由于哮喘与 CRS 和胃食管反流病都有关联,因此将其作为中介变量。此外还进行了敏感性测试。结果显示磁共振分析表明,遗传预测的胃食管反流与 CRS 风险增加有关(P < .001)。多变量 MR 分析显示,胃食管反流对 CRS 的影响相对独立。中介分析显示,哮喘对这一关联起中介作用,中介效应为 21.07%(95% CI,2.70%-40.18%)。敏感性分析未发现任何显著的多义性和异质性影响。结论我们发现遗传预测的胃食管反流病与 CRS 风险增加之间存在因果关系。作为中介因素,哮喘有助于胃食管反流病对 CRS 的影响。这项研究为预防 CRS 提供了高质量的因果证据。
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