The effects of micronutrients on the risk of upper gastrointestinal diseases: a two-sample Mendelian randomization study

PURPOSE: This study investigates the causal relationship between 12 micronutrients and 6 upper gastrointestinal diseases using a two-sample Mendelian randomization (MR) approach. METHODS: Genome-wide association studies (GWAS) summary data for upper gastrointestinal diseases were obtained from FinnGen, and micronutrient data were sourced from the IEU OpenGWAS database. The primary analysis method was inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode methods. Radial MR and iterative leave-one-out analyses were performed to identify and remove outlier single nucleotide polymorphisms (SNPs), and sensitivity analyses were conducted to assess the stability and reliability of the results. RESULTS: The MR analysis of IVW results revealed significant causal associations between genetically predicted selenium (OR = 1.08, 95% CI 1.01-1.15, P = 0.02) and vitamin B12 (OR = 0.60, 95% CI 0.43-0.83, P = 0.003) with chronic gastritis. After outlier removal, several previously non-significant associations became statistically significant: potassium with gastric ulcer (OR = 0.64, P = 0.030), zinc with gastric ulcer (OR = 1.12, P = 0.009), selenium with gastroesophageal reflux disease (OR = 1.05, P = 0.038), and vitamin B6 with gastric cancer (OR = 0.36, P = 0.018). All significant findings remained robust across sensitivity analyses, with no evidence of heterogeneity or horizontal pleiotropy after outlier removal. CONCLUSION: This MR study suggests that genetically predicted selenium levels may increase chronic gastritis risk, while vitamin B12 may be protective. Novel associations were identified for potassium, zinc, selenium, and vitamin B6 after outlier removal, providing new insights into the roles of micronutrients in upper gastrointestinal diseases.