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Genetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks [gRNA]

GSE296620 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/05/19 Platform GPL30173
Summary
Genetic variants associated with autoimmune diseases are highly enriched within putative cis-regulatory regions of CD4+ T cells, suggesting that they alter disease risk via changes in gene regulation. However, very few genetic variants have been shown to affect T cell gene expression or function. Here, we tested >18,000 autoimmune disease-associated variants for allele-specific expression using massively parallel reporter assays in primary human CD4+ T cells. We find 545 variants that modulate expression in an allele-specific manner (emVars). Primary T cell emVars greatly enrich for probable causal variants, are mediated by common upstream pathways, and their putative target genes are highly enriched within a lymphocyte activation network. Using bulk and single-cell CRISPR-interference screens, we confirm that emVar-containing T cell cis-regulatory elements modulate both known and previously unappreciated target genes that regulate T cell proliferation, providing plausible mechanisms by which these variants alter autoimmune disease risk.
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Direct links to NCBI, no account and no request form: the whole study as GSE296620_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1260251 and SRA study SRP583802. Searching any of these in the dataset finder brings you back here.

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