PT - JOURNAL ARTICLE AU - Alasoo, Kaur AU - Rodrigues, Julia AU - Mukhopadhyay, Subhankar AU - Knights, Andrew J. AU - Mann, Alice L. AU - Kundu, Kousik AU - , AU - Hale, Christine AU - Dougan, Gordon AU - Gaffney, Daniel J. TI - Genetic effects on chromatin accessibility foreshadow gene expression changes in macrophage immune response AID - 10.1101/102392 DP - 2017 Jan 01 TA - bioRxiv PG - 102392 4099 - http://biorxiv.org/content/early/2017/01/26/102392.short 4100 - http://biorxiv.org/content/early/2017/01/26/102392.full AB - Noncoding regulatory variants play an important role in the genetics of complex traits. Although quantitative trait locus (QTL) mapping is a powerful approach to identify these variants, many genetic effects may remain unobserved when cells are sampled in only one of a large number of possible environments. Using a novel induced pluripotent stem cell-derived system, we mapped QTLs regulating chromatin accessibility and gene expression in macrophages in four conditions mimicking the interplay between interferon-gamma response and Salmonella infection. We found that approximately 50% of condition-specific effects on gene expression altered chromatin accessibility prior to stimulation. Furthermore, 6% of the chromatin accessibility QTLs regulated multiple neighbouring regions and these interactions were modulated by stimulation, occasionally producing condition-specific changes in gene expression. Profiling additional states also doubled the number of expression QTLs that could be confidently colocalised with disease associations. Thus, a substantial fraction of disease-associated variants may affect ‘primed’ regulatory elements in naive cells.