Best practices in DNA methylation: lessons from inflammatory bowel disease, psoriasis and ankylosing spondylitis

Advances in genomic technology have enabled a greater understanding of the genetics of common immune-mediated diseases such as ankylosing spondylitis (AS), inflammatory bowel disease (IBD) and psoriasis. The substantial overlap in genetically identified pathogenic pathways has been demonstrated between these diseases. However, to date, gene discovery approaches have only mapped a minority of the heritability of these common diseases, and most disease-associated variants have been found to be non-coding, suggesting mechanisms of disease-association through transcriptional regulatory effects.Epigenetics is a major interface between genetic and environmental modifiers of disease and strongly influence transcription. DNA methylation is a well-characterised epigenetic mechanism, and a highly stable epigenetic marker, that is implicated in disease pathogenesis. DNA methylation is an under-investigated area in immune-mediated diseases, and many studies in the field are affected by experimental design limitations, related to study design, technical limitations of the methylation typing methods employed, and statistical issues. This has resulted in both sparsity of investigations into disease-related changes in DNA methylation, a paucity of robust findings, and difficulties comparing studies in the same disease.In this review, we cover the basics of DNA methylation establishment and control, and the methods used to examine it. We examine the current state of DNA methylation studies in AS, IBD and psoriasis; the limitations of previous studies; and the best practices for DNA methylation studies. The purpose of this review is to assist with proper experimental design and consistency of approach in future studies to enable a better understanding of the functional role of DNA methylation in immune-mediated disease.