Causal effect of urinary sodium-to-creatinine ratio on gastrointestinal diseases: A two-sample Mendelian randomization study

Given the epidemiological evidence suggesting an association between sodium intake and various gastrointestinal (GI) disorders, this study aimed to investigate the causal effect of genetically predicted urinary sodium-to-creatinine ratio (UNaUCr), a proxy for sodium intake, on GI diseases. Employing a Mendelian Randomization (MR) approach, genetic variants closely associated with UNaUCr were identified by extracting data from genome-wide association studies (GWAS). To validate the results, a comprehensive set of statistical methodologies, encompassing inverse-variance weighted (IVW), weighted median, and MR-Egger approaches was employed. Moreover, sensitivity analysis was performed, encompassing examinations of heterogeneity, investigations into horizontal pleiotropy, MR-PRESSO, and leave-one-out analysis. The findings of the IVW method indicated a positive causal association between genetically predicted UNaUCr and 2 GI traits: diseases of the esophagus, stomach, and duodenum (odds ratio = 1.76; 95% confidence interval [CI]: 1.35, 2.30), and irritable bowel syndrome (IBS) (odds ratio = 3.05; 95% CI: 1.64, 5.65). These associations remained significant after false discovery rate (FDR) correction. Other GI outcomes showed no significant associations after multiple testing correction. Results from weighted median and MR-Egger analyses were generally consistent. Although no substantial evidence of horizontal pleiotropy or heterogeneity was detected, residual pleiotropy cannot be completely excluded. This MR study provides evidence supporting a potential causal association between genetically predicted UNaUCr and 2 GI traits after FDR correction. However, as UNaUCr is a proxy for sodium intake and residual pleiotropy cannot be entirely excluded, these findings should be interpreted with caution and require further validation.