196: Impact of Chromatin Accessibility QTLs Across Immune Contexts

️ Episode 196: Impact of Chromatin Accessibility QTLs Across Immune Contexts In this episode of PaperCast Base by Base, we explore how single-cell chromatin accessibility QTLs (caQTLs) reshape the interpretation of immune disease genetics by mapping regulatory variation across major immune cell types and disease-relevant states. Study Highlights:The authors harmonized ∼280,000 PBMC scATAC-seq profiles from 48 individuals—including healthy donors and COVID-19 patients—to build a unified chromatin accessibility atlas. Topic modeling uncovered continuous cell-state programs, including a CD8 effector-memory continuum associated with COVID-19, and enabled the discovery of 37,390 caQTLs plus thousands of dynamic, state-dependent effects. Compared to eQTLs, caQTLs explained roughly 50% more GWAS loci and highlighted that many regulatory variants act through chromatin without detectable steady-state expression changes in current datasets. Extensive sharing of caQTLs across immune cell types contrasted with the context specificity of eQTL colocalizations, underscoring the need to integrate chromatin, expression, enhancer–promoter links, and disease-relevant cellular states to pinpoint causal mechanisms. Conclusion:Chromatin accessibility QTLs substantially expand the fraction of disease loci with molecular support, but reliable causal gene mapping requires convergence of caQTL and eQTL signals within the same cellular context and along relevant cell-state trajectories. Music:Enjoy the music based on this article at the end of the episode. Reference:Mu Z, Randolph HE, Aguirre-Gamboa R, Ketter E, Dumaine A, Locher V, Brandolino C, Liu X, Kaufmann DE, Barreiro LB, Li YI. Impact of disease-associated chromatin accessibility QTLs across immune cell types and contexts. Cell Genomics. 2026;6:101061. https://doi.org/10.1016/j.xgen.2025.101061 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:If you'd like to support Base by Base, you can make a one-time or monthly donation here: https://basebybase.com/

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