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The causal relationship between alcohol and urolithiasis remains uncertain, despite previous observational studies reporting an association between the two. To determine the causality, we conducted a two-sample Mendelian randomization (MR) analysis. In this study, we aimed to investigate the causal relationship between alcohol and kidney stones using a two-sample MR approach. Two sets of genetic instruments were utilized in the analysis, both of which were derived from publicly available genetic summary data. The first set consisted of 73 single-nucleotide polymorphisms (SNPs) robustly linked to alcohol intake frequency (AIF) and the second set was comprised of 69 SNPs associated with alcohol consumption (AC). Our MR analysis was performed using several methods including the inverse-variance weighted (IVW) method, weighted median method, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test. Our results from the MR analysis revealed a borderline significant association between AIF and the risk of urolithiasis. This was established through the use of the IVW method (OR (95% CI) = 1.29 (1.02, 1.65), p = 0.036) and the weighted median approach (OR (95% CI) = 1.44 (1.10, 1.89), p = 0.008). The MR-Egger model also yielded similar risk estimates (OR (95% CI) = 1.39 (0.66, 2.93), p = 0.386), although the relationship was not statistically significant. Sixty-eight SNPs were identified as having a substantial and independent link with AC. However, the IVW approach revealed no significant effect of AC on the risk of urolithiasis (OR (95% CI) = 0.74 (0.48, 1.14), p = 0.173). The MR analysis suggested a potential causal association between alcohol intake frequency and the risk of urolithiasis, but not alcohol consumption., (© 2023. The Author(s).)