ArticleAnnals of neurology2021
Genetic Variation in WNT9B Increases Relapse Hazard in Multiple Sclerosis.
Article in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2023Pooled it
- EBNA1Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Genetic Prognostic Factors in Multiple Sclerosis: Key Discoveries and Unmet Needs.International journal of molecular sciences · 2026Review
- Dysregulated circRNA-miRNA-mRNA networks reveal stage-specific mRNA expression changes in Parkinson's disease.Molecular brain · 2025Article
- Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.Annals of neurology · 2025Article
- Limited overlap between genetic effects on disease susceptibility and disease survival.Nature genetics · 2025Article
- Brain Atrophy and Cognitive Impairment in Primary and Secondary Progressive Multiple Sclerosis Cohort-Similar Progressive MS Phenotype.International journal of molecular sciences · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion.Journal of neurology · 2025Review
- Genetic Contribution to Medium-Term Disease Activity in Multiple Sclerosis.Molecular neurobiology · 2025Article
- Correlates and trajectories of relapses in relapsing-remitting multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Multiple sclerosis progression: time for a new mechanism-driven framework.The Lancet. Neurology · 2023Review
- Ensemble machine learning identifies genetic loci associated with future worsening of disability in people with multiple sclerosis.Scientific reports · 2022Article
- Toward Precision Phenotyping of Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2022Review
- Towards a global view of multiple sclerosis genetics.Nature reviews. Neurology · 2022Review
- Effects of Vitamin D and Body Mass Index on Disease Risk and Relapse Hazard in Multiple Sclerosis: A Mendelian Randomization Study.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Genetics and functional genomics of multiple sclerosis.Seminars in immunopathology · 2022Review
- WNT9A and WNT9B in Development and Disease.Differentiation; research in biological diversityReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveMany multiple sclerosis (MS) genetic susceptibility variants have been identified, but understanding disease heterogeneity remains a key challenge. Relapses are a core feature of MS and a common primary outcome of clinical trials, with prevention of relapses benefiting patients immediately and potentially limiting long-term disability accrual. We aim to identify genetic variation associated with relapse hazard in MS by analyzing the largest study population to date.
methodsWe performed a genomewide association study (GWAS) in a discovery cohort and investigated the genomewide significant variants in a replication cohort. Combining both cohorts, we captured a total of 2,231 relapses occurring before the start of any immunomodulatory treatment in 991 patients. For assessing time to relapse, we applied a survival analysis utilizing Cox proportional hazards models. We also investigated the association between MS genetic risk scores and relapse hazard and performed a gene ontology pathway analysis.
resultsThe low-frequency genetic variant rs11871306 within WNT9B reached genomewide significance in predicting relapse hazard and replicated (meta-analysis hazard ratio (HR) = 2.15, 95% confidence interval (CI) = 1.70-2.78, p = 2.07 × 10
interpretationGenetic factors underlying disease heterogeneity differ from variants associated with MS susceptibility. Our findings imply that genetic variation within the Wnt signaling and vitamin D pathways contributes to differences in relapse occurrence. The present study highlights these cross-talking pathways as potential modulators of MS disease activity. ANN NEUROL 2021;89:884-894.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.