The causal association between smoking, alcohol consumption and risk of upper urinary calculi: insights from a Mendelian randomization study

Background: The causal link between smoking, alcohol consumption, and upper urinary calculi remains uncertain in observational studies due to confounding factors. To uncover potential causal associations, we utilized two-sample univariable and multivariable Mendelian randomization (MR) methods.Methods: Five risk factors related to lifestyles (cigarettes per day, lifetime smoking index, smoking initiation, drinks per week and alcohol intake frequency) were chosen from the Genome-Wide Association Study (GWAS). Upper urinary calculi were obtained from the FinnGen and United Kingdom Biobank consortium. Inverse-variance-weighted (IVW) was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). While diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger.Results: The summary OR for upper urinary calculi was 0.6 (IVW 95% CI: 0.49-0.74; p = 1.31 x 10-06) per standard deviation decrease in drinks per week. Interestingly, the genetically predicted alcohol intake frequency was associated with a significantly increased risk upper urinary calculi (OR = 1.27; 95% CI: 1.11-1.45; p = 0.0005). Our study found no association between smoking initiation, the number of cigarettes per day, and the lifetime smoking index and the risk of upper urinary calculi. By adjusting for body mass index and education, estimates of drinks per week remained consistent in multivariate MR analyses, while alcohol intake frequency became non-significant.Conclusion: MR analysis showed that drinks per week was negatively associated with upper urinary calculi, whereas the effect of tobacco on upper urinary calculi was not significant and the detrimental effect of alcohol intake frequency on upper urinary calculi became non-significant after adjusting for BMI and education.