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Updated: Apr 14, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Brain MRI iron deposition and serum iron with multiple sclerosis: Evidence from a Mendelian randomization study
Tao Wu1, Lihua Wang2, Yuze Cao3
1Department of Neurology, Peking University First Hospital, Beijing, China.
Background:
Accumulating evidence suggests abnormal iron deposition in the brains of patients with multiple sclerosis (MS). However, the causal relevance of brain iron deposition, as well as its relationship with systemic iron status, remains uncertain.
Methods:
To investigate potential causal associations, we conducted Mendelian randomization (MR) analyses using summary data from the International Multiple Sclerosis Genetics Consortium (47,429 MS cases and 68,374 controls), brain quantitative susceptibility mapping (QSM, N = 35,273) and serum iron (163,511). Sensitivity analyses and bidirectional MR were conducted to fortify MR findings.
Results:
MS exhibited higher genetically predicted iron deposition in multiple brain regions, including the thalamus, caudate, and white matter hyperintensities (all p < 0.05). Among these, the association in the right thalamus (β = 0.028, 95% CI: [0.009, 0.047], p = 0.004) remained significant after Bonferroni correction for multiple comparisons (p < 0.05/9 = 5.55 × 10⁻³). Conversely, MS demonstrated lower genetically predicted serum iron concentration (β = -0.009, 95% CI: [-0.018, -0.001], p = 0.023). Multiple sensitivity analyses displayed relatively robust results, and bidirectional MR excluded reverse causal relationships.
Conclusion:
The study demonstrates a causal association between MS and increased brain iron deposition, particularly in the thalamus, as well as a separate association with decreased serum iron levels. These findings provide further insight into the relationship between MS and iron metabolism.
Insights
Multiple sclerosis (MS) is causally linked to increased brain iron deposition, especially in the thalamus. This study also found MS is associated with lower serum iron levels, clarifying iron metabolism
Area of Science:
- Neuroscience
- Genetics
- Iron Metabolism
Background:
- Abnormal brain iron deposition is observed in multiple sclerosis (MS) patients.
- The causal role of brain iron and its link to systemic iron status in MS are unclear.
Purpose of the Study:
- To investigate the causal relationship between MS and brain iron deposition.
- To explore the association between MS and systemic iron status.
Main Methods:
- Mendelian randomization (MR) analyses were performed using large-scale genetic data.
- Data included International Multiple Sclerosis Genetics Consortium, brain quantitative susceptibility mapping (QSM), and serum iron levels.
- Sensitivity analyses and bidirectional MR were employed to validate findings.
Main Results:
- Multiple sclerosis showed a genetic predisposition for higher iron deposition in brain regions like the thalamus, caudate, and white matter hyperintensities.
- The association between MS and iron deposition in the right thalamus remained significant after correction.
- Conversely, MS was genetically linked to lower serum iron concentrations.
Conclusions:
- A causal link exists between multiple sclerosis and increased brain iron deposition, particularly in the thalamus.
- MS is also causally associated with decreased serum iron levels.
- These findings enhance understanding of iron metabolism's role in MS pathogenesis.
