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

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.