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

ABSTRACT: Genetic variants associated with autoimmune diseases are highly enriched within putative cis-regulatory regions of CD4⁺ T cells, suggesting that they could alter disease risk through 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 effects on 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 likely causal variants, are mediated by common upstream pathways and their putative target genes are highly enriched within a lymphocyte activation network. Using bulk

SUBMITTER: Ho CH 

PROVIDER: S-EPMC12513834 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature