Aims and Hypotheses: This study will examine whether altered methylation status of regulatory genes involved in adaptive immunity contributes to the initiation and/or persistence of RA, by aiming to identify DMRs using the following strategies:-1.Whether DMRs can be identified which are related to the presence of active RA will be investigated. 2.Whether a subset of DMRs are associated with predisposition to/initiation of RA will be investigated, by comparing methylation patterns in blood samples obtained from ALSPAC maternal controls during pregnancy, with those from those participants who were disease free at the time, but went on to develop RA. 3.Whether genetic risk factors for RA act by predisposing to altered methylation will be addressed by examining whether methylation differences identified above as being associated with RA, are related to specific single nucleotide polymorphisms.

Outcomes: Genome-wide methylation will be analysed in early and late blood samples from 1000 ALSPAC maternal controls using the 450k illumina methylation platform as part of the ARIES study. The same method will be used to analyse early and late blood samples from ALSPAC mothers found to have RA, and blood samples from local RA cases. Genome-wide SNPs will be available, imputed to the latest version of hapmap, in ALSPAC cases and controls.