Causal association between rheumatoid arthritis and periodontitis: A Mendelian randomization study

This study investigates the causal relationship between rheumatoid arthritis (RA) and periodontitis (PD) using Mendelian randomization (MR) analysis in an East Asian population. This study employed a 2-sample MR analysis using genome-wide association study (GWAS) data. Single nucleotide polymorphisms (SNPs) associated with RA were selected from a GWAS dataset of 22,515 East Asian individuals (4873 RA cases and 17,642 controls). The association of these SNPs with PD was examined in a separate GWAS dataset of 212,453 East Asian individuals (3219 PD cases and 209,234 controls). The study utilized inverse variance weighted (IVW) analysis, MR-Egger regression, and the weighted median method to assess the causal effect of RA on PD. The IVW analysis demonstrated a statistically significant but modest inverse association between genetically predicted RA and PD risk (odds ratio = 0.931, 95% confidence interval 0.886-0.978, P = .005). No statistical evidence of directional horizontal pleiotropy was detected in the MR-Egger regression (Egger intercept = -0.005, P = .821), and Cochran Q test did not indicate substantial heterogeneity across instruments (P = .168). The direction and magnitude of the association were broadly consistent across the different MR methods applied. Leave-one-out sensitivity analyses did not identify any single SNP that disproportionately influenced the overall estimates. In this 2-sample Mendelian randomization study of East Asian populations, genetically predicted RA liability showed a statistically significant but modest inverse association with PD risk. The observed inverse association should be considered hypothesis-generating and does not provide definitive evidence that RA is protective against PD; further studies in other populations are needed to validate these findings and clarify the underlying mechanisms.