SINGLE CELL ANALYSIS OF GUT BIOPSY TISSUE REVEALS CELL TYPE- AND INFLAMMATION-SPECIFIC EXPRESSION QUANTATIVE TRAIT LOCI IN CROHN'S DISEASE

Genome-wide association studies have linked more than 320 genetic loci to IBD, however how these genetic risk factors lead to disease progression remains largely unknown. The advent of RNA-seq allowed us to link genetic variants to gene expression via expression Quantative Trait Loci (eQTLs), which have proven to be linked to disease phenotypes. The overlap between genetic variants that are linked to IBD, and the ones that affect gene expression unfortunately is quite poor. We hypothesize that this happens because cell-specific effects in the bulk RNA-Seq data are masked.

We here employ single cell RNA-seq of 159 gut biopsy samples (100 non-inflamed and 59 inflamed) and Global Screen Array genotyping from 151 corresponding individuals suffering from Crohn’s Disease to observe 4,149 eQTL effects at a cell-type-specific level.

We identified 3,396 independent loci, affecting the expression of 3,231 unique genes, across 11 different cell types. 10 of these loci are within Crohn’s disease risk loci. We have subsequently tested these independent effects to see which eQTLs occur upon inflammation, and found that 721 of these effects are modulated by both cell type specificity and tissue status.

These results show how genetic variation contributes to IBD and could support precision medicine applications