Abstract
INTRODUCTION: Existing research suggests an association between smoking and the incidence of recurrent aphthous stomatitis (RAS); however, the causal relationship remains ambiguous. We employed Mendelian randomization (MR) to clarify the potential causal association between smoking and the risk of developing RAS. METHODS: We utilized genome-wide association study (GWAS) sequencing data related to smoking from the Finnish database as instrumental variables (IVs) and GWAS data for RAS from the UK Biobank (UKB) as the outcome to perform a two-sample MR analysis. The selection of IVs was rigorously controlled according to the three principal assumptions of relevance, independence, and exclusivity. The primary analytical methods utilized were inverse variance weighting (IVW) and weighted median (WM), supplemented by MR-Egger, simple mode, and weighted mode techniques to infer causality between smoking and RAS. Sensitivity analyses were conducted using MR-PRESSO, Cochran's Q, and the MR-Egger intercept to ensure the robustness of the findings. RESULTS: The findings from the IVW and WM analyses suggest a causal association between smoking and an elevated risk of RAS (IVW: OR=1.003; 95% CI: 1.0002-1.005, p=0.033; WM: OR=1.003; 95% CI: 1.00006-1.007, p=0.044). Compared to non-smokers, smokers have a 0.3% increase in the risk of RAS. Furthermore, the sensitivity analysis did not reveal any inconsistencies that would contradict the MR results. CONCLUSIONS: Our findings provide preliminary evidence of a potential causal relationship between smoking and the risk of RAS, which may contribute to a deeper understanding of the underlying mechanisms. Further research is needed to confirm these results and explore their implications for clinical practice.