Hélène Perée, Viacheslav A Petrov, Yumie Tokunaga, Alexander Kvasz, Frédéric Farnir, Sophie Vieujean, Sarah Regimont, Myriam Mni, Marie Wéry, Samira Azarzar, Sophie Jacques, Nicolas Fouillien, Latifa Karim, Manon Deckers, Emilie Detry, Alice Mayer, Raafat Stephan, Keith Harshman, Yasutaka Mizoro, Catherine Reenaers, Catherine Van Kemseke, Odile Warling, Virginie Labille, Sophie Kropp, Maxime Poncin, Anne Catherine Moreau, Benoit Servais, Jean-Philippe Loly, SYSCID Consortium, BRIDGE Consortium, Wouter Coppieters, Emmanouil Dermitzakis, Edouard Louis, Michel Georges, Haruko Takeda, Souad Rahmouni
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.