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Updated: May 12, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Multiple sclerosis susceptibility loci do not alter clinical and MRI outcomes in clinically isolated syndrome
T Kalincik1, C R G Guttmann, J Krasensky
1Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic. tomas.kalincik@unimelb.edu.au
Abstract:
It has not yet been established whether genetic predictors of multiple sclerosis (MS) susceptibility also influence disease severity and accumulation of disability. Our aim was to evaluate associations between 16 previously validated genetic susceptibility markers and MS phenotype. Patients with clinically isolated syndrome verified by positive magnetic resonance imaging (MRI) and cerebrospinal fluid findings (n=179) were treated with interferon-β. Disability and volumetric MRI parameters were evaluated regularly for 2 years. Sixteen single-nucleotide polymorphisms (SNPs) previously validated as predictors of MS susceptibility in our cohort and their combined weighted genetic risk score (wGRS) were tested for associations with clinical (conversion to MS, relapses and disability) and MRI disease outcomes (whole brain, grey matter and white matter volumes, corpus callosum cross-sectional area, brain parenchymal fraction, T2 and T1 lesion volumes) 2 years from disease onset using mixed-effect models. We have found no associations between the tested SNPs and the clinical or MRI outcomes. Neither the combined wGRS predicted MS activity and progression over 2-year follow-up period. Power analyses confirmed 90% power to identify clinically relevant changes in all outcome variables. We conclude that the most important MS susceptibility loci do not determine MS phenotype and disease outcomes.
Insights
Genetic markers predicting multiple sclerosis (MS) susceptibility do not influence disease severity or disability accumulation. This study found no association between 16 MS susceptibility SNPs and clinical or MRI outcomes over two years.
Area of Science:
- Neurology
- Genetics
- Immunology
Background:
- The relationship between genetic susceptibility markers for multiple sclerosis (MS) and disease progression remains unclear.
- Understanding these genetic influences is crucial for predicting MS phenotype and disability.
- Previous studies have identified susceptibility loci, but their impact on disease severity needs further investigation.
Purpose of the Study:
- To investigate the association between 16 validated MS susceptibility genetic markers and MS phenotype.
- To evaluate the influence of these genetic markers on clinical and MRI-derived disease outcomes over a 2-year period.
Main Methods:
- A cohort of 179 patients with clinically isolated syndrome (CIS) treated with interferon-beta was studied.
- Sixteen single-nucleotide polymorphisms (SNPs) and a weighted genetic risk score (wGRS) were analyzed.
- Clinical outcomes (conversion to MS, relapses, disability) and MRI parameters (brain volumes, lesion loads) were assessed over 2 years using mixed-effect models.
Main Results:
- No significant associations were found between the 16 MS susceptibility SNPs and clinical or MRI outcomes.
- The combined weighted genetic risk score (wGRS) did not predict MS activity or progression.
- Statistical power analyses confirmed the study's ability to detect clinically relevant changes.
Conclusions:
- The major genetic loci associated with MS susceptibility do not appear to determine the disease phenotype or long-term outcomes.
- Genetic susceptibility markers may not be reliable predictors of disease severity or disability accumulation in MS.
- Further research may be needed to identify genetic factors influencing MS progression.
