Causal Relationships of 38 Risk Factors with Chronic Rhinosinusitis: A Mendelian Randomization Study

Abstract

Abstract Background At present, the identification of risk factors associated with chronic rhinosinusitis (CRS) remains elusive. Our goal was to systematically investigate modifiable risk factors linked to CRS. Methods We conducted univariable Mendelian randomization (MR) based on genome-wide association studies (GWAS) to assess the causal relationships between 38 risk factors and CRS. The primary statistical analysis employed the inverse variance weighted (IVW) method, complemented by MR Egger and weighted median methods, in addition to multiple sensitivity analyses. Following this, we performed multivariable MR to consider the potential confounding effects of gastroesophageal reflux disease (GERD) and evaluate direct causal relationships between risk factors and CRS. Results Univariable MR results indicated that cigarettes per day, short sleep duration, overall health rating (OHR), hypertension, allergic rhinitis (AR), GERD, bronchial asthma (asthma), atopic dermatitis (AD), and rheumatoid arthritis (RA) were linked to an increased risk of CRS. Conversely, coffee intake, years of schooling, and apolipoprotein A-I were associated with a reduced risk of CRS. No other risk factors showed an association with CRS. When we adjusted for GERD using multivariable MR, the associations of OHR, RA, asthma, AD, and RA with CRS remained statistically significant. However, the previously observed effects of cigarettes per day, coffee intake, short sleep duration, years of schooling, apolipoprotein A-I, and hypertension were no longer apparent. Conclusions Our study suggests direct causal relationships between genetically predicted OHR, RA, asthma, AD, and increased risk of CRS. These findings will significantly contribute to advancing the exploration of CRS etiology.