This could be a new biomarker.
Whole-blood methylation signatures are associated with and accurately classify multiple sclerosis disease severity
https://clinicalepigeneticsjournal.biom ... 22-01397-2
Abstract
Background
The variation in multiple sclerosis (MS) disease severity is incompletely explained by genetics, suggesting genetic and environmental interactions are involved. Moreover, the lack of prognostic biomarkers makes it difficult for clinicians to optimise care. DNA methylation is one epigenetic mechanism by which gene–environment interactions can be assessed. Here, we aimed to identify DNA methylation patterns associated with mild and severe relapse-onset MS (RMS) and to test the utility of methylation as a predictive biomarker.
Methods
We conducted an epigenome-wide association study between 235 females with mild (n = 119) or severe (n = 116) with RMS. Methylation was measured with the Illumina methylationEPIC array and analysed using logistic regression. To generate hypotheses about the functional consequence of differential methylation, we conducted gene set enrichment analysis using ToppGene. We compared the accuracy of three machine learning models in classifying disease severity: (1) clinical data available at baseline (age at onset and first symptoms) built using elastic net (EN) regression, (2) methylation data using EN regression and (3) a weighted methylation risk score of differentially methylated positions (DMPs) from the main analysis using logistic regression. We used a conservative 70:30 test:train split for classification modelling. A false discovery rate threshold of 0.05 was used to assess statistical significance.
Results
Females with mild or severe RMS had 1472 DMPs in whole blood (839 hypermethylated, 633 hypomethylated in the severe group). Differential methylation was enriched in genes related to neuronal cellular compartments and processes, and B-cell receptor signalling. Whole-blood methylation levels at 1708 correlated CpG sites classified disease severity more accurately (machine learning model 2, AUC = 0.91) than clinical data (model 1, AUC = 0.74) or the wMRS (model 3, AUC = 0.77). Of the 1708 selected CpGs, 100 overlapped with DMPs from the main analysis at the gene level. These overlapping genes were enriched in neuron projection and dendrite extension, lending support to our finding that neuronal processes, rather than immune processes, are implicated in disease severity.
Conclusion
RMS disease severity is associated with whole-blood methylation at genes related to neuronal structure and function. Moreover, correlated whole-blood methylation patterns can assign disease severity in females with RMS more accurately than clinical data available at diagnosis.
blood methylation is associated with severity
A forum to discuss research on the origins of MS and its development.
Return to “MS Etiology and Pathogenesis”
Jump to
- Multiple Sclerosis
- ↳ General Discussion
- ↳ Introductions
- ↳ Drug Pipeline
- ↳ Regimens
- ↳ Undiagnosed
- ↳ MS Etiology and Pathogenesis
- Treatments
- ↳ Chronic Cerebrospinal Venous Insufficiency (CCSVI)
- ↳ Low Dose Naltrexone
- ↳ Tysabri (Antegren, Natalizumab)
- ↳ Copaxone
- ↳ Glatopa
- ↳ Avonex
- ↳ Rebif
- ↳ Betaseron
- ↳ Plegridy
- ↳ Novantrone
- ↳ Aimspro
- ↳ Diet
- ↳ Stem Cells
- ↳ Antibiotics
- ↳ Campath (Lemtrada, Alemtuzumab)
- ↳ Gene Therapy
- ↳ Natural Approach
- ↳ Biotin (Qizenday, Cerenday, MD1003)
- ↳ Coimbra High-Dose Vitamin D Protocol
- ↳ Statins
- ↳ Tcelna (Tovaxin)
- ↳ Revimmune (Cyclophosphamide, Cytoxan)
- ↳ Medical Devices
- ↳ Rituxan (Rituximab)
- ↳ Ocrevus (Ocrelizumab)
- ↳ Kesimpta (Ofatumumab)
- ↳ Briumvi (Ublituximab-xiiy)
- ↳ General Medications
- ↳ Tecfidera (BG-12, Dimethyl fumarate)
- ↳ Vumerity (Diroximel fumarate)
- ↳ Bafiertam (Monomethyl fumarate)
- ↳ Gilenya
- ↳ Aubagio (Teriflunomide)
- ↳ Mayzent (Siponimod)
- ↳ Zeposia (Ozanimod)
- ↳ Ponvory (Ponesimod)
- ↳ Mavenclad (Cladribine)
- ↳ Ampyra (Dalfampridine)
- ↳ Medical Marijuana
- ↳ Sativex
- ↳ Chiropractic Treatment
- Life
- ↳ Daily Life
- ↳ Veterans and MS
- ↳ Trigeminal Neuralgia in MS
- ↳ Reading Nook
- ↳ Humor
- ↳ Shopping
- ↳ Friends and Family
- ↳ Mental & Spiritual Health
- ↳ Exercise and Physical Therapy
- ↳ Under 25 with MS
- ↳ MS in the Golden Years
- ↳ Parenting Kids With MS
- ↳ Parents with MS
- ThisIsMS.com
- ↳ Site Support
- ↳ Suggestions