ArticleNeurology. Genetics2016
Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.
Article in Neurology. Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials.Scientific reports · 2023Pooled it
- Genetic Risk in Multiple Sclerosis: Susceptibility, Modifiers and Unresolved Questions.Neurology and therapy · 2026Review
- Lifespan Modeling of Choroid Plexus Volume in Multiple Sclerosis and Its Dynamic Associations With Clinical, MRI, and HLA Susceptibility.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Immune-Related Gene Variants as Modifiers of Multiple Sclerosis Severity.International journal of molecular sciences · 2026Article
- Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs.International journal of molecular sciences · 2026Review
- Genetic Risk Variants for Multiple Sclerosis and Other Loci Linked to Intrathecal Immunoglobulin G Synthesis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Article
- Disentangling the heterogeneity of multiple sclerosis through identification of independent neuropathological dimensions.Acta neuropathologica · 2024Article
- Article
- New Insights into Risk Genes and Their Candidates in Multiple Sclerosis.Neurology international · 2022Review
- The role of the ZEB1-neuroinflammation axis in CNS disorders.Journal of neuroinflammation · 2022Review
- Ensemble machine learning identifies genetic loci associated with future worsening of disability in people with multiple sclerosis.Scientific reports · 2022Article
- Role of Multiple Vitamin D-Related Polymorphisms in Multiple Sclerosis Severity: Preliminary Findings.Genes · 2022Observational
- FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis.BMJ open · 2022Observational
- Single nucleotide variants around the connective tissue growth factor (CTGF/CCN2) gene and their association with multiple sclerosis risk, disability scores, and rate of disease progression.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- Genetics and functional genomics of multiple sclerosis.Seminars in immunopathology · 2022Review
- Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2021Article
- Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis.Biomolecules · 2021Review
- HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data.Scientific reports · 2021Article
- Little evidence for an effect of smoking on multiple sclerosis risk: A Mendelian Randomization study.PLoS biology · 2020Article
Corrections and comments
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Authors and funding
34 authors.
Funding
Abstract
objectiveWe investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS).
methodsTen unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01.
resultsA total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing.
conclusionsThe largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.