Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases
Nature Genetics. 2019-9-23;51:1486–1493.
- Abstract
- Immune-disease-associated variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states is unknown. Here we stimulated T cells and macrophages in the presence of 13 cytokines and profiled active and open chromatin regions. T cell activation induced major chromatin remodeling, while the presence of cytokines fine-tuned the magnitude of changes. We developed a statistical method that accounts for subtle changes in the chromatin landscape to identify SNP enrichment across cell states. Our results point towards the role of immune-disease-associated variants in early rather than late activation of memory CD4+ T cells, with modest differences across cytokines. Furthermore, variants associated with inflammatory bowel disease are enriched in type 1 T helper (TH1) cells, whereas variants associated with Alzheimer’s disease are enriched in different macrophage cell states. Our results represent an in-depth analysis of immune-disease-associated variants across a comprehensive panel of activation states of T cells and macrophages.
- Consortium data used in this publication
- ATAC-seq: EGAS00001003501; H3K27ac: EGAS00001002749
- Datasets
- DSR635MPW, DSR175BHN, DSR091EHR, DSR569SMG, DSR670HLZ, DSR385RBR, DSR357SSF, DSR312KJD, DSR389ARJ, DSR438DZY, DSR771YJD, DSR388DTJ, DSR379KAZ, DSR595CRI, DSR205VKL, DSR218CVO, DSR090BHY, DSR273HMQ, DSR445OJG, DSR595RJZ, DSR981HFQ, DSR187VES, DSR109LNN, DSR599QYF, DSR357BAD, DSR278DAU, DSR797DLL, DSR540FCW, DSR474WZB, DSR527QSP, DSR633BOI, DSR301SBT, DSR363BEM, DSR556QBQ, DSR251UQX, DSR556GSU, DSR314OSF, DSR999CYT, DSR978EZR, DSR219WDW, DSR088HGB, DSR170PAX, DSR861WEB, DSR564SXP, DSR250YOF, DSR491OZE, DSR005JUP, DSR782INO, DSR759IVM, DSR139MNQ, DSR918MVB, DSR793OTH, DSR060SQK, DSR154SYT, DSR616NJF, DSR738JIP, DSR862EWK, DSR559VCR, DSR374HIO, DSR734QNA, DSR333WAS, DSR462TOM, DSR692KOA, DSR088AIJ, DSR876MUU, DSR160CDF, DSR973CTB, DSR308AYD, DSR975OAF, DSR332EPW, DSR599GJL, DSR122IAA, DSR258QDL, DSR585WBF, DSR396PZA, DSR026SKX, DSR965CLE, DSR880RHX, DSR313CSC, DSR023ZPD, DSR650AME, DSR911ZMH, DSR224KYT, DSR131IUH, DSR296MCB, DSR561UPU, DSR700APQ, DSR827OPP, DSR177WMK, DSR579XCD, DSR074YJV, DSR980OUB, DSR997WOC, DSR462VPA, DSR719BCU, DSR978QZC, DSR195ELE, DSR332YVR, DSR772JZF, DSR746XRA, DSR723FAX, DSR634VEB, DSR920RWG, DSR250CPX, DSR885VKD, DSR997NEY, DSR963RVA, DSR673ZVL, DSR430FNW, DSR533HZD