_Genetics_of_gene_expression_in_macrophage_immune_response_Open_access

We differentiated macrophages from induced pluripotent stem cells in 86 unrelated, healthy individuals derived by the Human Induced Pluripotent Stem Cells Initiative (HIPSCI), and profiled gene expression and chromatin accessibility in four experimental conditions: naive, interferon-gamma (IFNy) treatment, Salmonella infection and IFNy treatment followed by Salmonella infection. We detected gene expression QTLs (eQTLs) for 5,383 genes, and chromatin accessibility QTLs (caQTLs) for 32,918 accessible regions, including hundreds of long-range interactions. We show that profiling even a small number of additional cellular states substantially increases the number of eQTLs that we can confidently colocalise with a known disease association, with approximately 30% new disease-eQTL pairs discovered in each additional state. Furthermore, we show that approximately 50% of stimulus-specific effects on gene expression manifest in naïve cells where they alter chromatin accessibility alone. Our results suggest that many disease-associated genetic variants lie in regulatory elements in a ‘primed’ state waiting for an appropriate environmental signal before regulating gene expression.

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