<p dir="ltr">This is a table of DNA methylation Beta values for individual participants in the study. The values range from 0 to 1, representing 0% methylation to 100% methylation. Raw data (idat files) were analysed in R using Bioconductor software packages [36]. The Minfi package [37] was used to preprocess raw signal intensities to methylation measurements, and also to detect any low-quality samples by inspecting the median of the methylated and unmethylated signal intensities. The SWAN (Subset-quantile Within Array Normalization) package [38] was used for probe type normalization by correcting for technical differences between type I and type II probes (which measure methylated and unmethylated signals using two paired probes, or use a single probe, respectively).Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4 T cell DNA methylation from 56 oligoarticular JIA (oJIA) cases and 57 age and sex matched controls using Illumina HumanMethylation450 arrays. DNA methylation at each array probe was tested for association with oJIA using RUV (Remove Unwanted Variation) together with a moderated t-test. Further to this ‘all-inclusive’ analysis, we stratified by age at diagnosis (?6yrs, >6yrs) and by sex as potential sources of heterogeneity. Following False Discovery Rate (FDR) adjustment, no probes were associated with oJIA in the all-inclusive, >6yrs-diagnosed, or sex-stratified analyses, and only one probe was associated with oJIA in the ?6yrs-diagnosed analysis. We attempted technical validation and replication of 14 probes (punadj<0.01) at genes of known/potential relevance to disease. At VPS53, we demonstrated a regional shift towards higher methylation in oJIA (all-inclusive) compared to controls. At REEP3, where polymorphism has been previously associated with JIA, we demonstrated higher DNA methylation in male oJIA compared to male controls. This is the most comprehensive JIA case-control analysis of DNA methylation to date. While we have generated some evidence of altered methylation in oJIA, substantial differences are not apparent in CD4þ T cells. This may indicate a lesser relevance of DNA methylation levels in childhood, compared to adult, rheumatic disease.</p>
History
MCRI Data Classification
Public
Domain Data Controller
Richard Saffery
Domain Data Steward
Richard Saffery
Provenance
This is a new dataset generated for a manuscript in 2018.