Increased DNA methylation variability in rheumatoid arthritis discordant monozygotic twins
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Authors
Paul, DS
Publication Date
2018-09-04Journal Title
Genome Medicine
ISSN
1756-994X
Publisher
Springer Nature
Volume
10
Issue
64
Language
eng
Type
Article
This Version
VoR
Metadata
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Paul, D. (2018). Increased DNA methylation variability in rheumatoid arthritis discordant monozygotic twins. Genome Medicine, 10 (64) https://doi.org/10.1186/s13073-018-0575-9
Abstract
Background: Rheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease discordant monozygotic twin pairs.
Methods: Genome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between RA and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.
Results: We have identified a differentially variable DNA methylation signature, that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.
Conclusions: Through genome-wide analysis of DNA methylation in disease discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.
Sponsorship
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
European Commission Horizon 2020 (H2020) Societal Challenges (733161)
Identifiers
External DOI: https://doi.org/10.1186/s13073-018-0575-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288549
Rights
Attribution 4.0 International (CC BY 4.0), Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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