Causal effects of metabolic traits on dental diseases: a comprehensive Mendelian randomization study

Introduction: Metabolic disorders have been linked to dental diseases, but whether these associations reflect causal effects remains unclear. This study aimed to investigate whether metabolic traits exert causal effects on dental diseases using a two-sample Mendelian randomization (MR) approach. Materials and methods: We conducted a two-sample MR study of 52 metabolic exposures from three East Asian biobanks (BioBank Japan, Korean Genome and Epidemiology Study, Taiwan Precision Medicine Initiative) and 31 scan outcomes from FinnGen, UK Biobank, and the genome-wide association study (GWAS) Catalog (1215 pairs after quality control); continuous-trait odds ratios are per 1 standard deviation (SD). Three Catalog files originally labelled as periodontitis were excluded from dental inference after source-file identity checks (GCST90018905/906/907), leaving 28 dental outcomes (1059 pairs). Instruments were genome-wide significant with stringent linkage disequilibrium (LD) clumping. Six MR methods, multivariable MR (MVMR), mediation analysis, colocalization, cross-ancestry comparison, and European-instrument replication were applied. Results: Seven associations survived false discovery rate (FDR) correction; six are dental and remain FDR-significant in the 1059-pair subset, led by body mass index (BMI) → pulpitis (odds ratio [OR] = 1.22 per 1 SD, p = 4.3 × 10 −10 ; replicated in two independent East Asian biobanks). Genetically predicted waist circumference was associated with higher dental caries risk (OR = 1.25–1.29), and inverse associations were observed for high-density lipoprotein cholesterol (HDL-C) (mouth ulcers; preliminary) and blood urea nitrogen (BUN) (caries). After mutual adjustment, BMI retained an association with pulpitis. Colocalization supported a shared signal at the FTO (fat mass and obesity-associated) gene (PP.H4 = 0.82–0.85), and European instruments replicated BMI → pulpitis ( p = 1.4 × 10 −51 ). Conclusions: Among dental outcomes, convergent MR, MVMR, colocalization, and European-instrument replication support an association consistent with a causal effect of adiposity on pulpitis and, more tentatively, on caries. Integration of oral-health surveillance into metabolic-disease care remains a hypothesis for trials. Replication in East Asian outcome datasets is warranted.