Differential DNA methylation in Multiple Sclerosis
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ABSTRACT:
PROVIDER: PRJNA417506 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide DNA methylation level was studied to determine whether multiple sclerosis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in peripheral blood from multiple sclerosis patients (cases) and normal controls
2018-04-20 | GSE106648 | GEO
Project description:Identification of differential DNA methylation associated with multiple sclerosis: a family-based study
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Project description:Genome wide DNA methylation profiling of genomic DNA isolated from hippocampus of multiple sclerosis patients were hybridized to Illumina HumanMethylation450 Beadchip arrays. DNA methylation profiles across approximately 45,000 CpGs were compared between 8 myelinated and 7 demyelinated tissues .
2017-09-14 | GSE101658 | GEO
Project description:Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis–affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts. Genes regulating oligodendrocyte survival, such as BCL2L2 and NDRG1, were hypermethylated and expressed at lower levels in multiple sclerosis–affected brains than in controls, while genes related to proteolytic processing (for example, LGMN, CTSZ) were hypomethylated and expressed at higher levels. These results were not due to differences in cellular composition between multiple sclerosis and controls. Thus, epigenomic changes in genes affecting oligodendrocyte susceptibility to damage are detected in pathology-free areas of multiple sclerosis–affected brains.
2013-11-24 | GSE40360 | GEO
Project description:Whole blood is a highly convenient and informative tissue from which to sample DNA and RNA in epigenomic and functional genomic studies, but it is comprised of multiple distinct cell types and this complexity significantly impairs our ability to interpret downstream differential methylation and/or differential expression results. In this multiple sclerosis (MS)-focused study we utilised an application of current statistical deconvolution methods to interrogate whole blood DNA methylation data thereby enabling the methylome of several immune cell types to be analysed independently. Methylome profiling on cell type-purified blood samples revealed optimal CpG sets for use as robust immune cell markers in the statistical deconvolution process. We show that it is possible to identify differentially methylated (DM) loci in a cell type specific manner using statistical deconvolution. Finally, we demonstrate that deconvolution improved the biological relevance and interpretability of our DM results, significantly enhancing concordance of the identified DM loci with loci previously shown to be genetically or epigenetically associated with MS.
2017-06-30 | GSE88824 | GEO
Project description:Multiple Sclerosis (MS) is known to be caused by a genetic predisposition triggered by environmental factors. Despite the knowledge of genetic factors and environmental agents involved, it is largely unclear how they interact. Epigenetics, particularly DNA methylation, represents a model for environmental factors to influence the genome. In this paper, we studied 26 affected and 26 unaffected relatives from 8 MS multiplex families (≥ 3 affected relatives) as part of a multicentric Italian cohort study using Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) run on an Illumina® HiSeq 2500 (2x100 bp). Technical validation in 6/8 of the original families and biological replication in 2 additional families (FDR < 0.1 and a concordant fold change, FC) were performed in suggestive differentially methylated regions (DMRs) between affected and unaffected relatives using SeqCap Epi Choice Enrichment (Roche®). Evidence of association from MeDIP-Seq across 8 families was combined with aggregation statistics, separately for hypo- and hyper-methylated regions with concordant FC in ≥ 6/8 families, yielding 162 DMRs at FDR ≤ 0.1. Technical validation and biological replication led to 2 hypomethylated regions, which point to NTM and BAI3 genes, and 2 hypermethylated regions in PIK3R1 and CAPN13 (mean size: 3.1 kb). Multiplex families represent a privileged setting for the study of regions of differential methylation as they reduce the impact of potential confounders like shared genetics and environmental factors. We identified 4 novel regions which contain genes of potential interest that need to be tested in larger cohorts of patients.
2021-05-01 | GSE149562 | GEO
Project description:The major histocompatibility complex (MHC) region represents by far the strongest multiple sclerosis (MS) susceptibility loci. DNA methylation changes have been consistently detected at the MHC region in MS. However, understanding the full picture of epigenetic regulations of MHC in MS remains challenging, due in part to the limited coverage in the region by standard whole genome bisulfite sequencing or array-based methods. To fill this gap, we utilized a novel but validated MHC capture protocol with bisulfite sequencing and conducted a comprehensive analysis of MHC methylation landscapes in blood samples from 147 treatment naïve MS participants and 129 healthy controls. We identified 132 differentially methylated region (DMRs) within MHC regions and found they are significantly overlapped with MS risk variants. Integration of the MHC methylome to human leukocyte antigen (HLA) genetic data further indicate that the methylation changes are significantly associated with HLA genotypes. Using DNA methylation quantitative trait loci (mQTL) mapping and the causal inference test (CIT), we identified 643 cis-mQTL-DMRs paired associations including 71 DMRs possibly mediating causal relationships between 55 SNPs and MS risk.
2023-11-28 | GSE235106 | GEO
Project description:Genome wide DNA methylation profiling of CD4 T cells from treated and untreated patients with multiple sclerosis. The Illumina InfiniumEPIC methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs of CD4 T cells from patients with multiple sclerosis.
2018-04-03 | GSE112596 | GEO
Project description:Patient with multiple sclerosis improves during pregnancy while temporarily worsening post-partum. The reasons behind the disease modulation during pregnancy remain unknown. In this study, we have investigated the effect of pregnancy on circulating CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls to gain a deeper understanding why patients with multiple sclerosis improves during pregnancy. We assessed epigenome-wide DNA methylation in CD4+ and CD8+ T cells obtained during (1st, 2nd and 3rd trimester) and after pregnancy (6 weeks post-partum), using the Infinium MethylationEPIC 850K array.
2023-09-23 | E-MTAB-12250 | biostudies-arrayexpress
Project description:Black and Hispanic American patients frequently develop earlier onset of multiple sclerosis (MS) and a more severe disease course that can be resistant to disease modifying treatments. The objectives were to identify differential methylation of genomic DNA (gDNA) associated with disease susceptibility and treatment responses in a cohort of MS patients from underrepresented minority populations. Patients with MS and controls with non-inflammatory neurologic conditions were consented and enrolled under an IRB-approved protocol. Approximately 64% of donors identified as Black or African American and 30% as White, Hispanic-Latino. Infinium MethylationEPIC bead arrays were utilized to measure epigenome-wide gDNA methylation of whole blood. Data were analyzed in the presence and absence of adjustments for unknown covariates in the dataset, some of which corresponded to disease modifying treatments. Global patterns of differential methylation associated with MS were strongest for those probes that showed relative demethylation of loci with lower M values. Pathway analysis revealed unexpected associations with shigellosis and amoebiasis. Enrichment analysis revealed an over-representation of probes in enhancer regions and an under-representation in promoters. In the presence of adjustments for covariates that included disease modifying treatments, analysis revealed 10 differentially methylated regions (DMR’s) with an FDR <1E-77. Five of these genes (ARID5B, BAZ2B, RABGAP1, SFRP2, WBP1L) are associated with cancer risk and cellular differentiation and have not been previously identified in MS studies. Hierarchical cluster and multi-dimensional scaling analysis of differential DNA methylation at 147 loci within those DMR’s was sufficient to differentiate MS donors from controls. In the absence of corrections for disease modifying treatments, differential methylation in patients treated with dimethyl fumarate was associated with immune regulatory pathways that regulate cytokine and chemokine signaling, axon guidance, and adherens junctions. These results demonstrate possible associations of gastrointestinal pathogens and regulation of cellular differentiation with MS susceptibility in our patient cohort. This work further suggests that analyses can be performed in the presence and absence of corrections for immune therapies. Because of their high representation in our patient cohort, these results may be of specific relevance in the regulation of disease susceptibility and treatment responses in Black and Hispanic Americans.
2023-02-07 | GSE219293 | GEO