Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases

Immune disease variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states is unknown. We stimulated T cells and macrophages in the presence of thirteen cytokines and profiled active and open chromatin regions. T cell activation induced major chromatin remodeling, while cytokines fine-tuned the magnitude of changes. We developed a statistical method that accounts for subtle changes in chromatin landscape to identify SNP enrichment across cell states. Our results point towards the role of immune disease variants in early rather than late activation of memory CD4+ T cells, with modest differences across cytokines. Furthermore, inflammatory bowel disease variants are enriched in Th1 cells while Alzheimer’s disease variants are enriched in different macrophage cell states. Our results represent an in-depth analysis of immune disease variants across a comprehensive panel of activation states of T cells and macrophages.