ArticleAnnals of neurology2025
Increased Disability Progression in rs10191329
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Rethinking prognosis in multiple sclerosis: a multiaxial perspective.Nature reviews. Neurology · 2026Review
- Donor-specific pathological features associate with genetic background, lesion type distribution, and clinical heterogeneity in multiple sclerosis.Acta neuropathologica · 2026Article
- Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs.International journal of molecular sciences · 2026Review
- Brain Atrophy Associated With Risk Variant rs10191329 Extends Beyond Multiple Sclerosis.Annals of neurology · 2026Article
- The rs10191329 Risk Allele Is Associated With Pronounced Retinal Layer Atrophy in Multiple Sclerosis.Annals of clinical and translational neurology · 2025Observational
- Clinical application of age-derived cut-offs for plasma neurofilament light chain in multiple sclerosis.Journal of neurology · 2025Article
- Multiple sclerosis severity variant iniScience · 2025Article
- Aggressive treatment of early acute focal inflammatory activity to extend the window for BTK inhibition in multiple sclerosis.Therapeutic advances in neurological disorders · 2025Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
objectiveWe examined the impact of the rs10191329 genetic risk variant on neuroaxonal damage as measured by serum neurofilament light chain (sNfL) levels, and disability progression in people with multiple sclerosis (pwMS).
methodsIn a cohort of pwMS (n = 740), 658 participants were prospectively monitored every 2 years for less than a decade while 82 of 740 pwMS were monitored retrospectively for up to 40 years. We investigated associations between rs10191329 variants and clinical outcome, including Expanded Disability Status Scale (EDSS), disability accrual (defined by EDSS-increase of at least 1.5 for patients starting at EDSS 0, at least 1.0 EDSS-points for patients with an initial EDSS between 1 and 4.5 and at least 0.5 points for patients starting with an EDSS equal or greater than 5) and progression to secondary progressive MS (SPMS). Clinical outcomes were analyzed using Kaplan-Meier and Cox proportional hazards analyses. Disability accumulation over time was depicted using a generalized mixed-effect model. Single-molecule array was used to assess sNfL levels.
resultsHomozygous, heterozygous, and non-carriers of the rs10191329 risk variant displayed comparable sNfL levels indicating similar neuroaxonal damage at the time of diagnosis. Importantly, in homozygous carriers we found highest sNfL levels in follow-up visits preceding elevated disease progression later in the disease course, a steeper increase in overall disability measures and higher probability of SPMS development.
interpretationThese findings highlight how genetic variants may serve as new biomarkers for disease progression and can be used for personalized medicine and risk assessment in MS. ANN NEUROL 2025;97:596-605.
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