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Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs
Valentina Ciampana1, Eleonora Virgilio2, Loredana Paciolla1
1Neurology Unit, Department of Translational Medicine, Maggiore Della Carità Hospital, University of Piemonte Orientale, 28100 Novara, Italy.
International Journal of Molecular Sciences
|May 4, 2026
Summary
Genetic factors influencing multiple sclerosis (MS) prognosis are modest and inconsistent. While some genome-wide association studies show promise, more research is needed to use genetic markers for personalized MS patient management.
Area of Science:
- Neuroimmunology
- Genetics
- Neurology
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease with variable clinical outcomes.
- Genetic factors are known to influence MS susceptibility, but their role in prognosis is less clear.
Purpose of the Study:
- To review current evidence on the genetic contribution to multiple sclerosis prognosis.
- To identify genetic factors associated with clinical, radiological, and biomarker outcomes in MS.
Main Methods:
- Structured narrative review of genetic studies in multiple sclerosis.
- Examination of genome-wide association studies (GWAS) and candidate-gene studies.
- Analysis of associations with age at onset, relapse rate, disability progression, lesion burden, and biomarkers.
Main Results:
- Genetic influences on MS prognosis are generally modest and heterogeneous.
- Limited replicated genetic associations exist; many findings lack confirmation.
- GWAS identified a locus in the DYSF-ZNF638 region for MS Severity Score and showed strongest evidence for relapse rate, MRI measures, and intrathecal IgG synthesis.
Conclusions:
- Current genetic markers are insufficient for routine prognostic stratification in MS.
- Larger collaborative studies and epigenetic research are needed to improve understanding and reproducibility.
- Identifying predictive genetic factors could enable personalized MS management and treatment approaches.
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