Cell-type specific analyses in blood and gut identify cis-eQTL matching 140 IBD risk loci and entrectinib as repurposing candidate.

Genes whose expression is affected, in a consistent manner, by GWAS-identified risk variants and the disease process, constitute preferred drug targets. We herein combine cis-eQTL analysis in 27 sorted blood cell populations and 43 intestinal cell types identified by single cell RNA-Seq in the ileum, colon and rectum, with information on gene expression in patients, to search for putative drug targets for inflammatory bowel disease. We detect >95 K cis-eQTL that affect >13 K e-genes and cluster in >24 K regulatory modules. We uncover matching regulatory modules for 140 risk loci, implicating >300 e-genes not previously connected with inflammatory bowel disease, and find 152 matching e-genes whose expression is perturbed in the blood or gut of patients. We identify entrectinib, a small molecule inhibiting the NRLP3 inflammasome by binding NEK7, as a possible repurposing candidate.