We used a massively parallel reporter assay (MPRA) to test thousands of autoimmune disease-associated genetic variants for allele-specific effects on gene expression in primary human T cells. Variants that altered gene expression within our MPRA were then linked to T cell regulatory networks and proliferation using bulk and single-cell CRISPR-interference screens.
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References
Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012). This paper demonstrates that autoimmune GWAS variants are enriched for cis-regulatory regions in T cells.
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Mouri, K. et al. Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells. Nat. Genet. 54, 603–612 (2022). This paper reports an MPRA performed in Jurkat cells that analyzed the same autoimmune variants as the primary T cell MPRA in this paper.
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This is a summary of: Ho, C.-H. et al. Genetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks. Nat. Genet. https://doi.org/10.1038/s41588-025-02301-3 (2025).
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Genetic perturbations link autoimmune risk variants to T cell function. Nat Genet 57, 2359–2360 (2025). https://doi.org/10.1038/s41588-025-02302-2
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DOI: https://doi.org/10.1038/s41588-025-02302-2