Gastroesophageal Reflux and Chronic Rhinosinusitis: A Mendelian Randomization Study

Objective Chronic rhinosinusitis (CRS) is associated with gastroesophageal reflux (GERD). However, the causal relationship is controversial. We conducted a two-sample Mendelian Randomization (MR) analysis to explore this potential association. Methods Based on genome-wide association studies (GWAS), a univariable MR was performed to explore the causal relationship of GERD with CRS. Instrumental variables (IVs) pertinent to anti-GERD treatment were employed as a means of validation. The primary MR outcome was established using an inverse variance weighted (IVW) method, supplemented by multiple sensitivity analyses. Subsequently, a multivariable MR was conducted to account for potential confounding variables, thereby ascertaining a direct effect of GERD on CRS. Finally, a network MR analysis was carried out to elucidate the mediating role of asthma in the relationship between GERD and CRS. Results The univariable MR demonstrated an association between GERD and an elevated risk of CRS (IVW OR = 1.30, 95% CI = 1.18–1.45, p = 4.19 × 10−7). Omeprazole usage was associated with a reduction in CRS risk (IVW OR = 0.64, 95% CI = 0.42–0.98, p = 0.039). The causal relationship between GERD and CRS remained after adjusting for potential confounders, such as smoking characteristics, body mass index, asthma, allergic rhinitis, in the multivariable MR analysis. Besides, the proportion of the causal effect of GERD on CRS mediated by asthma was 19.65% (95% CI = 2.69%–36.62%). Conclusion GERD was independently associated with an increased risk of CRS. The mediating role of asthma between GERD and CRS also reveals that GERD is one of the mechanisms underlying unified airway disease. Level of Evidence 3 Laryngoscope, 2024