Assessment of bidirectional relationships between circulating cytokines and periodontitis: Insights from a mendelian randomization analysis.

The purpose of this Mendelian randomization (MR) study was to assess the causal relationship between circulating cytokines and periodontitis. Based on the aggregated statistics of the largest publicly available genome-wide association study (GWAS), we applied a bidirectional two-sample MR. MR analyses were conducted using Inverse variance weighted (IVW), Robust Adjusted Profile Score (RAPS), Maximum likelihood (ML), Weighted median and MR-Egger, and results obtained from IVW served as the primary outcome. Cochran Q test was used to test the heterogeneity. MR-Egger intercept test and MR polymorphism residual and outlier test (MR-PRESSO) were used for polymorphism analysis. Leave-one-out sensitivity and funnel plots were used for sensitivity analysis. The IVW method indicated that interleukin 9 (IL9) had a positive causal relationship with periodontitis [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.049-1.372, = 0.008], and interleukin 17 (IL17) had a negative causal relationship with periodontitis (OR = 0.847, 95% CI = 0.735-0.976, = 0.022). In bidirectional MR, periodontitis was not causally related to any of the cytokines in our study. Our findings provided evidence in support of potential causal associations between circulating IL9/IL17 and periodontitis.