Genetic Causal Association between Rheumatoid Arthritis and Periodontitis: A Bidirectional Two-Sample Mendelian Randomization Analysis

Abstract

Abstract Background A link between rheumatoid arthritis (RA) and periodontitis (PD) has been established. However, their causal relationship remains unclear and the effect of different serotypes of RA on the PD development has not been investigated. This study aims to elucidate the causal association between PD and different serotypes of RA using Mendelian Randomization (MR). Methods A bidirectional two-sample MR analysis was performed using available large-scale genome-wide association studies statistics. The inverse-variance weighted (IVW) or multiplicative random-effects IVW was used to determine causality, depending on the heterogeneity of instrumental variables. Additional sensitivity analyses were also performed. Results The forward MR analysis identified that seropositive RA [odds ratio (OR):1.26, 95% confidence interval (CI): 1.07–1.44, p = 0.0018], but not seronegative RA [OR:1.01, 95% CI: 0.95–1.06, p = 0.9098], was associated with an increased risk of PD. The reverse MR analysis did not show any significant causal effect of PD on RA, independent of the serotypes. The sensitivity tests (p > 0.05) confirmed the robustness and accuracy of these findings. Conclusion This study revealed that there was a genetic causal effect of seropositive RA on PD, suggesting that this subtype of RA patients may require specific clinical attention to prevent the development of PD.