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.