Abstract
Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation arerecognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure andinherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNAmethylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. Afterprioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of amajor effect CpG island in DRB1 in MS cases (pFDR <3 x 10-3). In addition, we found 55 non-HLA CpGs that exhibiteddifferential methylation, many of which localise to genes previously linked to MS.Conclusions: Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation toMS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.
| Original language | English |
|---|---|
| Pages (from-to) | 1033-1041 |
| Number of pages | 9 |
| Journal | Multiple Sclerosis |
| Volume | 20 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2014 |
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Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis. / Graves, Moira C.; Benton, Miles C.; Lea, R. A.; Boyle, Frances M.; Tajouri, L.; Macartney-Coxson, D.; Scott, Rodney J.; Lechner-Scott, Jeannette.
In: Multiple Sclerosis, Vol. 20, No. 8, 2014, p. 1033-1041.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Methylation differences at the HLA-DRB1 locus in CD4+ T-Cells are associated with multiple sclerosis
AU - Graves, Moira C.
AU - Benton, Miles C.
AU - Lea, R. A.
AU - Boyle, Frances M.
AU - Tajouri, L.
AU - Macartney-Coxson, D.
AU - Scott, Rodney J.
AU - Lechner-Scott, Jeannette
PY - 2014
Y1 - 2014
N2 - Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation arerecognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure andinherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNAmethylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. Afterprioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of amajor effect CpG island in DRB1 in MS cases (pFDR <3 x 10-3). In addition, we found 55 non-HLA CpGs that exhibiteddifferential methylation, many of which localise to genes previously linked to MS.Conclusions: Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation toMS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.
AB - Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk ofdeveloping MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation arerecognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure andinherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNAmethylation analysis of CD4+ T cells from 30 patients with relapsing-remitting MS and 28 healthy controls using Illumina450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p21, with a peak signal at HLA-DRB1. Afterprioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of amajor effect CpG island in DRB1 in MS cases (pFDR <3 x 10-3). In addition, we found 55 non-HLA CpGs that exhibiteddifferential methylation, many of which localise to genes previously linked to MS.Conclusions: Our findings provide the first evidence for association of DNA methylation at HLA-DRB1 in relation toMS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.
UR - http://www.scopus.com/inward/record.url?scp=84904820156&partnerID=8YFLogxK
U2 - 10.1177/1352458513516529
DO - 10.1177/1352458513516529
M3 - Article
VL - 20
SP - 1033
EP - 1041
JO - Multiple Sclerosis
JF - Multiple Sclerosis
SN - 1352-4585
IS - 8
ER -