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GI highlights from the literature

BASIC SCIENCE Inflammation status modulates the effect of host genetic variation on intestinal gene expression in IBD Hu S, Uniken Venema W, Westra H et al. Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease. Nat Commun 2021; 121: 1122. IBD is a complex disease with more than 240 genetic risk loci identified so far. However, little is known about how they contribute to disease development in tissue level. Using snapfrozen biopsies from 112 inflamed and 168 noninflamed intestinal tissues, Hu et al studied how genetic variants influenced transcription of closeby genes through cisexpression quantitative trait loci (ciseQTL) using RNA sequencing and genotyping by whole exome sequencing and genomewide genotyping. A total of 190 inflammationdependent intestinal ciseQTLs including known IBDrisk genes and genes encoding immunecell receptors and antibodies were found. The intestinal ciseQTLs are inflammationdependent and certain eQTLs coexpressed with IBDassociated genes, indicating that inflammationdependent ciseQTLs are potentially involved in gene–gene interactions. Among the 190 inflammationdependent intestinal ciseQTLs, 125 of them showed a significant interaction with celltype enrichment, illustrating that inflammationdependent eQTLs might be partially driven by enrichment of specific cell types. Moreover, the inflammationdependent intestinal ciseQTLs demonstrated genetic susceptibility under inflammatory conditions. By targeting these inflammationdependent eQTLs, a new therapy, which is highly specific to both tissues and disease status, can be developed, allowing precision medicine in IBD.