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We need new drugs for IBD. Currently, 1 in 123 people suffer from Crohn’s, ulcerative colitis or some form of IBD in the UK, but there is no cure, and existing drugs can be ineffective or lose efficacy over time.

Genetics are a good starting point for drug development, but while Genome Wide Association Studies have nominated loci for IBD, only a fraction of these have successfully been linked to causal genes with current eQTL discovery methods, which often rely on bulk RNA sequencing of heterogeneous tissues

3/6/26, 3:10 pm0 reposts0 likes

@tobioinformatics.bsky.social @bradleyomics.bsky.social hypothesised that colocalising GWAS signals with cell-type-specific single-cell eQTLs would more readily nominate disease effector genes, since regulators active only in specific cellular contexts are more likely to escape purifying selection

To test this hypothesis, they generated the largest collection of single-cell RNA sequencing data from IBD-relevant sites (terminal ileum, rectum, blood), resulting in nearly 2.2 million single-cell transcriptomes from over 400 individuals including 125 with IBD.

By mapping eQTLs at three progressively higher resolutions, they found over 84,000 eQTLs in 251 cellular annotations. Notably, many eQTLs were only found at higher resolutions, and cell-type-level eQTLs were more than twice as likely to colocalise with IBD GWAS loci than tissue-level eQTLs.