TY - JOUR T1 - Genetic effects on chromatin accessibility foreshadow gene expression changes in macrophage immune response JF - bioRxiv DO - 10.1101/102392 SP - 102392 AU - Kaur Alasoo AU - Julia Rodrigues AU - Subhankar Mukhopadhyay AU - Andrew J. Knights AU - Alice L. Mann AU - Kousik Kundu AU - HIPSCI Consortium AU - Christine Hale AU - Gordon Dougan AU - Daniel J. Gaffney Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/26/102392.abstract N2 - 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. ER -