eQTL in diseased colon tissue identifies potential target genes associated with IBD.

Genome-wide association studies (GWAS) have identified over 300 loci associated with the inflammatory bowel diseases (IBD), but putative causal genes for most loci are unknown. We conducted a disease-focused expression quantitative trait loci (eQTL) analysis using colon tissue from 252 IBD patients. We hypothesized IBD tissue could uncover IBD-associated regulatory variation undetectable in non-IBD cohorts. Here we show a total of 194 potential target genes for 108 IBD loci using eQTL from both IBD and non-IBD colon tissue. eQTL in IBD tissue were enriched for IBD GWAS colocalizations, provided evidence for genes such as ABO and TNFRSF14, and identified additional potential target genes compared to non-IBD tissue eQTL alone. Our results suggest disease state may alter the regulatory landscape and its characteristics, leading to increased effect sizes for some eQTL. These findings highlight the importance of diseased tissue eQTL studies for identifying potential consequences of IBD-associated variants.