Causal relationships between potential risk factors and chronic rhinosinusitis: a bidirectional two-sample Mendelian randomization study

Purpose Smoking, alcohol consumption, allergic rhinitis (AR), asthma, and obesity are associated with chronic rhinosinusitis (CRS), albeit the causal relationships between them remain elusive. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate the bidirectional causal effects between these potential risk factors and CRS.Methods The data for daily cigarette consumption, age of smoking initiation, weekly alcohol consumption, AR, asthma, body mass index (BMI), and CRS were drawn from large sample size genome-wide association studies. Single-nucleotide polymorphisms associated with each exposure were considered instrumental variables in this study. We investigated causal effects by using the inverse-variance weighted (IVW) method with random effects, and weighted median and MR-Egger methods were used for sensitivity analyses. Pleiotropic effects were detected and corrected by the MR pleiotropy residual sum and outlier test and MR-Egger model.Results We found the causal effects of daily cigarette consumption (IVW, OR = 1.15, 95% CI 1.00-1.32, p = 0.046), AR (IVW, OR = 4.77, 95% CI 1.61-14.13, p = 0.005), asthma (IVW, OR = 1.45, 95% CI 1.31 - 1.60, p < 0.001), and BMI (IVW, OR = 1.05, 95% CI 1.00-1.09,p = 0.028) on CRS. Furthermore, we found a causal effect of CRS on asthma (IVW OR = 1.08, 95% CI 1.05-1.12, p < 0.001).Conclusions We confirmed the causal effects of daily cigarette consumption, AR, asthma, and BMI on CRS, and the causal effect of CRS on asthma, while no causal relationship between age of smoking initiation, weekly alcohol consumption, and CRS was found. These findings are expected to provide high-quality causal evidence for clinical practice and the pathogen-esis of CRS and asthma.