Utilizing a two-sample Mendelian randomization analysis, this study investigated the potential link between chronic rhinosinusitis (CRS) and gastroesophageal reflux disease (GERD)

Leveraging genome-wide association studies (GWAS), researchers conducted a univariable Mendelian randomization to probe the causal link between GERD and CRS. Instrumental variables related to anti-GERD treatment were employed for validation. The primary Mendelian randomization analysis utilized an inverse variance weighted (IVW) method, complemented by multiple sensitivity analyses.

Subsequently, a multivariable Mendelian randomization was performed to adjust for potential confounders, establishing a direct GERD-CRS relationship. Lastly, a network Mendelian randomization analysis was undertaken to shed light on asthma's mediating role in the GERD-CRS connection.

The findings of the univariable Mendelian randomization revealed a link between GERD and a heightened CRS risk (IVW Odds ratio [OR] = 1.30, 95% Confidence Interval [CI] = 1.18-1.45, p = 4.19 × 10-7 ). As found, Omeprazole usage was related to a reduced CRS risk (IVW OR = 0.64, 95% CI = 0.42-0.98, p = 0.039). Even after adjusting for potential confounders such as allergic rhinitis, smoking habits, asthma, and body mass index in the multivariable Mendelian randomization, the GERD-CRS causal connection persisted. Moreover, asthma was found to mediate 19.65% (95% CI = 2.69%-36.62%) of the causal effect of GERD on CRS.

GERD exhibited an independent connection with an elevated CRS risk. The mediation of asthma in the GERD-CRS relationship suggested GERD as one of the mechanisms contributing to unified airway ailment.