Causal relationship of serum micronutrient with autoimmune neurological diseases: a Mendelian randomization study

Background The relationship between micronutrients and autoimmune neurological diseases such as multiple sclerosis (MS), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) remains poorly understood. This study aims to elucidate the causal relationships between specific micronutrients and these diseases using Mendelian randomization (MR) analysis with publicly available genome-wide association study (GWAS) data. Methods We utilized data from Open GWAS to identify genetic instruments associated with 15 micronutrients, including copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, zinc, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, and vitamin E in European populations. For outcome data, we sourced GWAS datasets from the Finnish database comprising 2409 MS cases and 408561 controls, 461 MG cases and 408430 controls, and 445 GBS cases and 405136 controls. Single nucleotide polymorphisms (SNPs) with P-values less than 5 × 10^-6 were selected as instrumental variables (IVs), ensuring minimal linkage disequilibrium. Statistical analysis was performed using inverse-variance weighted (IVW) method complemented by weighted mode, weighted median estimate, MR-Egger regression, and simple mode approaches. Sensitivity analyses included Cochran's Q test for heterogeneity, MR-Egger intercept and MR-PRESSO for horizontal pleiotropy, and the one-by-one exclusion method for assessing the influence of specific SNPs on the MR analysis results. Results Our findings indicate a significant inverse association between blood magnesium levels and MS risk (OR = 0.47; 95% CI: 0.27–0.81; P = 0.007). Similarly, blood iron levels showed a significant inverse association with MG risk (OR = 0.19; 95% CI: 0.04–0.87; P = 0.032). No statistically significant causal relationships were observed between any of the studied micronutrients and GBS. Conclusion In conclusion, our MR analysis suggests that higher blood levels of magnesium may reduce the risk of MS and higher blood levels of iron may reduce the risk of MG. These findings warrant further investigation into the potential therapeutic roles of these micronutrients in autoimmune neurological diseases. Future research should focus on elucidating the underlying biological mechanisms and exploring potential clinical applications based on these associations.