Single-cell atlas links IBD risk to cell-type specific gene regulation

Researchers built IBDverse, the largest single-cell eQTL atlas for inflammatory bowel disease, mapping cis-eQTL effects across blood and gut tissues in about 400 individuals to link genetic risk to specific cell types. They find cell-type eQTLs are more distal, enhancer-rich, and far more likely to colocalize with IBD GWAS signals than bulk-tissue eQTLs, nominating effector genes such as MAML2 and ZMIZ1 in dendritic cells and MYC and RASGRP1 in colonocytes. Notch pathway regulators in dendritic cells and Wnt-driven epithelial renewal in colonocytes emerge as key mechanisms, tying regulatory variation to barrier dysfunction and inflammation. The study also highlights therapeutic angles—including PRKCB inhibitors and targets like ITGA4/JAK2—and provides a framework for interpreting GWAS loci via cell-type–resolved eQTL mapping in complex diseases.