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Potential Causal Relationships Between Circulating Micronutrient Levels and Multiple Neuroimmune Diseases: A Genetic
Longhao Chen1,2,3, Xuzhou Wu4, Kaizheng Wang1,2,3
1The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Brain and Behavior
|September 9, 2025
Summary
This study used Mendelian randomization to find causal links between micronutrients and neuroimmune diseases. Specific micronutrients like magnesium, folate, vitamin B6, and iron show causal associations with conditions such as multiple sclerosis and myasthenia gravis.
Area of Science:
- Neuroimmunology
- Nutritional Science
- Human Genetics
Background:
- Circulating micronutrient levels are increasingly linked to neuroimmune diseases, but causal relationships remain uncertain.
- Confounding factors obscure the roles of many implicated micronutrients in these conditions.
- Understanding these links is crucial for neuroimmune disease etiology and management.
Purpose of the Study:
- To establish the causal relationship between circulating micronutrient levels and neuroimmune diseases using genetic association analysis.
- To investigate the regulatory role of micronutrients in the development and progression of neuroimmune diseases.
- To identify specific micronutrients causally linked to various neuroimmune conditions.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was employed.
- Fourteen micronutrients were selected from genome-wide association studies (GWAS).
- Seven neuroimmune diseases (MS, GBS, ADEM, AP, SP, ON, MG) data were analyzed from the FinnGen database (5523 cases, 2,860,006 controls) using inverse variance weighting (IVW) and sensitivity analyses.
Main Results:
- Significant causal associations were found between specific micronutrients and neuroimmune diseases.
- Multiple sclerosis (MS) showed a causal link with magnesium levels (OR: 0.467).
- Acute disseminated encephalomyelitis (ADEM) was linked to folate (OR: 0.022), optic neuritis (ON) to vitamin B6 (OR: 0.382), and myasthenia gravis (MG) to iron (OR: 0.194).
- Sensitivity analyses confirmed the robustness of these findings, with no significant pleiotropy or heterogeneity detected.
Conclusions:
- This study confirms causal relationships between specific micronutrients and neuroimmune diseases.
- Findings offer novel insights into the etiology of neuroimmune diseases.
- Provides a theoretical foundation for micronutrient-based prevention and treatment strategies for neuroimmune disorders.
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