Potential Association Between Basal Metabolic Rate and Presbyopia: A Two-Sample Mendelian Randomisation Study

Background/Objectives: Basal metabolic rate (BMR) is implicated in age-related phenotypes, and presbyopia represents a hallmark of ocular ageing. However, the association between BMR and presbyopia remains underexplored. Therefore, using a two-sample Mendelian randomisation (MR) approach, the present study aimed to evaluate the potential causal relationship between BMR and presbyopia in individuals of European ancestry. Methods: Instrumental variables comprised single-nucleotide polymorphisms associated with BMR at genome-wide significance (p < 5.0 × 10^-8), derived from genome-wide association study summary statistics from the UK Biobank. Summary statistics for presbyopia were obtained from the FinnGen project. Causal estimates were primarily assessed using the inverse-variance weighted method and further evaluated using the weighted median method, MR-Egger regression, and the MR-Pleiotropy Residual Sum and Outlier test. Results: Genetically predicted higher BMR, expressed per 1-standard-deviation increase on the inverse-rank-normalised scale, was associated with lower odds of presbyopia. The inverse-variance weighted analysis yielded an odds ratio (OR) of 0.79 (95% confidence interval [CI]: 0.67-0.93; p = 0.004), with a directionally consistent estimate from the weighted median analysis (OR = 0.76, 95% CI: 0.59-0.99; p = 0.045). MR-Egger and SIMEX-corrected MR-Egger analyses yielded estimates in the same inverse direction, although their 95% CIs included the null (OR = 0.73, 95% CI: 0.50-1.05; p = 0.093 and OR = 0.71, 95% CI: 0.47-1.06; p = 0.092, respectively). The MR-PRESSO global test was nominally significant (p = 0.049), although no individual outlier was identified. In additional MVMR analyses incorporating BMI or standing height, the direct effect of BMR was not statistically significant in either model. Conclusions: These findings suggest a potential inverse association between higher genetically predicted BMR and the odds of presbyopia. However, MVMR analyses did not support a direct effect of BMR independent of BMI or height, warranting caution in interpreting the observed association as specific to metabolic rate. Further studies are required to validate these results and clarify the underlying biological mechanisms.