Associations involving distant genes (trans-eQTL, defined as SNPs >1 Mb from the probe) may define gene networks regulated by specific SNPs and can provide unbiased insights into pathway identity and underlying biological processes. It is unclear whether the relative paucity of trans-eQTL observed in human eQTL studies, usually attributable to limited power, may also reflect that many trans networks are undetectable in baseline states (21). Our genome-wide eQTL mapping across stimuli in the full data sets, correcting for multiple testing, resolved a total of 1838 trans-associating genes at FDR <0.05 (394 genes at P < 5 × 10−12, approximate to Bonferroni-corrected P = 0.05). Trans-associating loci showed a high degree of context specificity—most notably after IFN-γ treatment when multiple novel trans-eQTLs were identified that were frequently unobservable in the naïve state (Fig. 2, fig. S8, and table S3). Several loci, such as the previously described 12q15 locus at LYZ (8, 22) and the major histocompatibility complex (MHC), showed significant trans associations across treatments, whereas other master regulatory SNPs were resolved only in LPS or IFNγ–induced cells and putatively driven by cis-eQTL modulating cytokine release, enzymes, and transcription factors (Fig. 2).
