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

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.