Potential Causal Relationships Between Circulating Micronutrient Levels and Multiple Neuroimmune Diseases: A Genetic Association Analysis

Abstract

Background

Growing evidence suggests a close association between circulating micronutrient levels and neuroimmune diseases. Nevertheless, the causal relationship between them remains unclear. Furthermore, due to confounding factors, many micronutrients implicated in these diseases remain unidentified. This study aimed to determine the causal relationship between circulating micronutrients and neuroimmune diseases through genetic association analysis, and to analyze the regulatory role of circulating micronutrients in neuroimmune diseases.

Method

In this study, we used a two-sample mendelian randomization (MR) analysis to explore the causal relationship between micronutrients levels and neuroimmune disease. Fourteen micronutrients were screened from a published genome-wide association study (GWAS). Neuroimmune diseases include multiple sclerosis (MS), Guillain–Barre syndrome (GBS), acute disseminated encephalomyelitis (ADEM), acute poliomyelitis (AP), sequelae of poliomyelitis (SP), optic neuritis (ON), and myasthenia gravis (MG). Data on these seven neuroimmune diseases came from the FinnGen database and included 5523 cases and 2,860,006 controls. The inverse variance weighting (IVW) method was used as the main MR analysis method, and sensitivity analysis was performed to determine MR hypotheses.

Results

Through MR analysis and sensitivity testing, we identified significant causal relationships between four neuroimmune diseases and micronutrient levels. Specifically, MS was causally associated with magnesium levels (OR: 0.467, 95% CI: 0.269–0.809, p = 0.007), ADEM with folate levels (OR: 0.022, 95% CI: 0.001–0.957, p = 0.047), ON with vitamin B6 levels (OR: 0.382, 95% CI: 0.187–0.778, p = 0.008), and MG with iron levels (OR: 0.194, 95% CI: 0.043–0.867, p = 0.032). Sensitivity analysis showed that there was no level pleiotropic or heterogeneity in our study results.

Conclusion

This study established the causal relationship between micronutrients and neuroimmune diseases. These findings provide new insights into the etiology of neuroimmune diseases and provide a theoretical basis for micronutrient regulation, prevention, and treatment of neuroimmune diseases.