Causal relationships between rhinosiusitis and gastroesophageal reflux disease： a bidirectional two-sample Mendelian randomization study

Abstract

Background Gastroesophageal reflux disease (GERD) is associated with acute and chronic rhinosinusitis (ARS/CRS), although the causal relationship between them is not clear. Methods We conducted a bidirectional two-sample Mendelian randomized study to investigate the causal effects between GERD and rhinosinusitis (RS). The data for GERD and RS were obtained from large sample size genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with each exposure were considered instrumental variables in this study. We conducted a causal effect analysis using the inverse-variance weighted (IVW)，Weighted median，MR Egger，Simple mode and Weighted mode methods. The inverse-variance weighted and MR - Egger methods were used for the heterogeneity analysis. The MR - Egger model method was adopted for Pleiotropic effects. Results MR analysis showed that GERD had a statistically significant causal effect on ARS (IVW, OR = 1.324, 95% CI 1.177-1.490, p <0.001) and CRS (IVW, OR = 1.365, 95% CI 1.185-1.572, p <0.001).MR analysis showed that CRS had a statistically significant causal effect on GERD (IVW, OR = 1.033, 95% CI 1.009-1.056, p =0.006). However, the MR-Egger model revealed the evidence of horizontal pleiotropy for the causal effect of CRS on GERD (Egger-intercept=0.007, p=0.032). In addition，we did not observe a causal effect of ARS on GERD (IVW, OR = 1.019, 95% CI 0.986-1.053, p=0.269). Conclusions We confirmed the causal effect of GRED on RS, while no causal effect of RS on GERD was found. These studies are expected to provide high-quality causal evidence for the pathogenesis of RS and GERD, and additional ideas for their primary prevention and treatment.