Inflammatory bowel disease is a chronic inflammatory bowel disorder. It is classified into two major entities: Ulcerative colitis (UC) and Crohn’s disease (CD), whose subtype identification is critical for correct disease management, especially for surgery and personalized treatment. Diagnosis is challenging, with approximately 10% of patients being classified as ‘indeterminate colitis’. Therefore, novel biomarkers for stratifying patients and improving diagnostics are highly needed.

Here, we have applied a unique RNA sequencing technique, Cap Analysis of Gene Expression (CAGE), on intestinal biopsies from 94 patients with IBD as well as healthy controls. This provided a genome wide atlas of active transcription start sites and enhancers. We show that highly expressed immune cell related transcripts were powerful predictors of the degree of inflammation (controls vs CD & UC), while lowly expressed epithelial cell related transcripts were far more powerful predictors of UC vs. CD. Using the enhancer atlas we show that enhancer transcription can distinguish the inflammatory state of patients and that similarly regulated enhancers and promoters share transcription factor binding sites. Utilizing GWAS data we show that enhancers are more enriched for the heritability of IBD than promoters.