We further interrogated trans associations to rs2275888 on a single SNP basis. This revealed that most associations occur after 24-hour LPS, with 17 genes in trans, many of which were archetypal early interferon response genes (Fig. 3, B and C, and table S4). Ingenuity pathway analysis (IPA) of trans-associated genes after LPS stimulation resolved an IFN-β–driven network and identified a key role for the upstream regulator IRF7 (P = 9.5 × 10−26) (Fig. 3D). Anti-viral response was the most significant disease and biological annotation (P = 1 × 10−16), whereas significant canonical pathways included interferon signaling (P = 5.8 × 10−8) and pattern recognition receptors (recognition of bacteria and viruses) (P = 6.7 × 10−08). This temporal relationship between a cis-eQTL and trans-associated gene network is consistent with the downstream consequences of differential IFN-β expression after LPS induction modulated by rs2275888.
