Blood-Derived DNA Methylation Signatures of Crohn’s Disease and Severity of Intestinal Inflammation

Crohn’s disease is a relapsing inflammatory disorder with a variable clinical course. While most patients present with purely an inflammatory phenotype (B1) at diagnosis, a subgroup (~20%) rapidly progresses to complicated disease manifestations that include stricturing (B2) within 5 years. DNA methylation is a key epigenetic mechanism that can regulate gene expression and thereby influence the development and progression of complex diseases. Site-specific DNA methylation differences have been reported in peripheral blood of patients with Crohn’s disease, but investigation of the temporal relationship between methylation and disease is required to establish whether the methylome plays a causal role and can be leveraged for therapeutic benefits. To this end, we conducted an epigenome-wide study of methylation (~850K sites) in peripheral blood at diagnosis and during follow-up from the RISK pediatric Crohn’s disease inception cohort. While some methylation changes associated with Crohn’s disease might be causal, in peripheral blood the vast majority are found to be a transient consequence of inflammation and thus a symptom of disease. DNA methylation was assessed in peripheral blood from pediatric non-IBD controls and patients with Crohn's disease at two time points - at diagnosis and follow-up. Peripheral blood DNA was extracted, bisulfite converted and genome-wide DNA methylation was interrogated using the HumanMethylationEPIC BeadChip (Illumina).