Genetic evidence for causal link between systemic inflammation and dental caries risk: A bidirectional Mendelian randomization study

The causal relationship between systemic inflammation and dental caries remains unclear. This study aimed to investigate the bidirectional causal association between circulating cytokines and the risk of dental caries. A bidirectional 2-sample Mendelian randomization (MR) study was conducted. Genetic instruments for 132 circulating cytokines were obtained from 2 large-scale genome-wide association study consortia (n = 8293 and n = 14,824). Summary statistics for dental caries were sourced from the FinnGen consortium (n = 1,95,395). The inverse variance weighted method was used for the primary analysis, supplemented by a range of sensitivity analyses (e.g., MR-Egger, weighted median, MR-PRESSO) to assess the robustness of the findings and detect horizontal pleiotropy. Genetically predicted higher levels of several cytokines were causally associated with an increased risk of dental caries, including CXCL9 (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.05–1.49 and CTACK (OR = 1.15, 95% CI: 1.04–1.27). Conversely, higher levels of IFN-γ (OR = 0.79, 95% CI: 0.65–0.96), IL-17 (OR = 0.83, 95% CI: 0.71–0.97), and RANTES (OR = 0.85, 95% CI: 0.76–0.96) were associated with a reduced risk. In the reverse analysis, genetic liability for dental caries was causally linked to increased levels of Artemin and decreased levels of Cystatin D and IL-2RA. Sensitivity analyses confirmed the robustness of these associations. Our findings reveal a bidirectional causal relationship between specific inflammatory cytokines and dental caries. This suggests that systemic inflammatory pathways both contribute to and are influenced by the pathogenesis of dental caries, highlighting potential biomarkers and therapeutic targets.