RT Journal Article SR Electronic T1 Genetic effects on chromatin accessibility foreshadow gene expression changes in macrophage immune response JF bioRxiv FD Cold Spring Harbor Laboratory SP 102392 DO 10.1101/102392 A1 Kaur Alasoo A1 Julia Rodrigues A1 Subhankar Mukhopadhyay A1 Andrew J. Knights A1 Alice L. Mann A1 Kousik Kundu A1 HIPSCI Consortium A1 Christine Hale A1 Gordon Dougan A1 Daniel J. Gaffney YR 2017 UL http://biorxiv.org/content/early/2017/01/26/102392.abstract 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.