Evidence for causal effects of serum trace minerals on risk of gastric diseases: A mendelian randomization study

Background The causal association of serum trace minerals with gastric diseases have investigated in several observational studies. However, the results are conflicting and establishing causality has always been a challenge due to potential residual confounding. We conducted this mendelian randomization (MR) analysis aiming to explain the causal effects of serum trace minerals on risk for gastric diseases. Methods 32 single nucleotide polymorphisms (SNPs) significantly associated with serum trace minerals (calcium, phosphorus, magnesium, iron, copper, selenium, zinc) in published genome-wide association studies (GWAS) were applied as instrumental variables (IVs). GWAS summary data for gastric diseases were obtained from the UK Biobank, the FinnGen consortium and Medical Research Council Integrative Epidemiology Unit (MRC-IEU) OpenGWAS project. Inverse variance weighted (IVW) was the main method of mendelian randomization (MR) analysis. Cochran’s Q statistics, Rucker’s Q test, MR-PRESSO and MR-Egger intercept were used to assess pleiotropy and heterogeneity. Results A protective effect of serum calcium against gastric polyp (IVW: OR: 0.989, 95%CI 0.981 − 0.971, p = 0.009) and a hazardous effect against chronic gastritis (IVW: OR: 1.008, 95%CI 1.001–1.016, p = 0.034; Weighted median: OR: 1.009, 95%CI 1.002–1.016, p = 0.009) were found. Genetically predicted serum magnesium was causally associated with increased risks of gastric polyp (Weighted median: OR: 1.040, 95%CI 1.020–1.064, p = 0.035) and gastric cancer (MR-Egger: OR: 3.3e + 17, 95%CI 1.9e + 10-5.9e + 24, p = 0.009). Suggestive associations with decreased risk of gastric polyp (IVW: OR: 0.998, 95%CI 0.997–0.999, p = 0.047) and gastric cancer (IVW: OR: 0.851, 95%CI 0.773–0.988, p = 0.035) were noted for genetically predicted serum iron. Genetic liability to serum selenium was significantly and inversely associated with gastric disorder (IVW: OR: 0.987, 95%CI 0.979–0.995, p = 0.002; Weighted median: OR: 0.988, 95%CI 0.979–0.998, p = 0.024), gastric ulcer (IVW: OR: 0.987, 95%CI 0.981–0.994, p = 0.0002; Weighted median: OR: 0.988, 95%CI 0.980–0.996, p = 0.003) and chronic gastritis (IVW: OR: 0.993, 95%CI 0.987–0.998, p = 0.012). Genetically predicted serum copper caused increased risk of gastric ulcer (IVW: OR: 1.001, 95%CI 1.000-1.002, p = 0.032). Causal relationships between zinc (p > 0.05), phosphorus (p > 0.05) and gastric diseases were not obtained. The reliability of the results was verified by sensitivity analysis. Conclusion The study provided MR evidence of causal associations of serum calcium, magnesium, iron, copper and selenium with gastric diseases. Specifically, a positive causal relationship was observed between serum magnesium levels and gastric cancer risk, while serum iron levels were inversely associated with gastric cancer.