Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins
Authors
Webster, Amy P
Plant, Darren
Ecker, Simone
Zufferey, Flore
Bell, Jordana T
Feber, Andrew
Paul, Dirk S
Beck, Stephan
Barton, Anne
Williams, Frances M K
Worthington, Jane
Publication Date
2018-09-04Type
Journal Article
Metadata
Show full item recordCitation
Webster, A. P., Plant, D., Ecker, S., Zufferey, F., Bell, J. T., Feber, A., Paul, D. S., et al. (2018). Increased DNA methylation variability in rheumatoid arthritis-discordant monozygotic twins. [Journal Article]. https://doi.org/10.1186/s13073-018-0575-9
Abstract
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 rheumatoid arthritis 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.
Identifiers
External DOI: https://doi.org/10.1186/s13073-018-0575-9
This record's DOI: https://doi.org/10.17863/CAM.26447
Rights
Rights Holder: The Author(s).
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