Association between clonal hematopoiesis and periodontitis: a two-sample mendelian randomization study

Clonal hematopoiesis (CH) is an age-associated phenomenon characterized by the proliferation of blood cells carrying somatic mutations. Recent studies suggest a potential link between CH and periodontitis, but the causal relationship remains unclear. A two-sample Mendelian randomization (MR) analysis was implemented, examining whether CH phenotypes are causally associated with periodontitis. CH phenotypes included overall clonal hematopoiesis (CH-overall), CH with a DNMT3A mutation (CH-DNMT3A), CH with a TET2 mutation (CH-TET2), large clones (CH-large), and small clones (CH-small). Genetic instruments were derived from genome-wide association studies, and the inverse-variance weighted (IVW) method was the primary analytical approach. Sensitivity analyses and reverse MR were also performed to ensure robustness. MR analysis demonstrated a significant association between CH-DNMT3A and periodontitis (odds ratio: 0.084, 95% CI: 0.007–0.972, P = 0.047), suggesting a protective role. No significant associations were found for other CH phenotypes. Reverse MR analyses showed no statistical evidence of a bidirectional relationship between periodontitis and any CH phenotype. Additionally, the analyses showed no signs of pleiotropy or heterogeneity that could confound the results. Our findings suggest a novel protective role for DNMT3A-mutated CH in periodontitis. Further research is warranted to explore the mechanisms underlying this association. © The Author(s) 2025.