Interindividual variation in the early (2 hours) and late (24 hours) inflammatory responses to lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls that triggers TLR4 signaling (10), and interferon-γ (IFN-γ) (24 hours), a cytokine acting through the JAK-STAT (Janus kinase–signal transducer and activator of transcription) signaling pathway, important in mycobacterial and viral infections (15, 16), was characterized in highly purified primary CD14+ human monocytes from 432 individuals of European ancestry. Genome-wide gene expression profiling and genotyping were performed with HumanHT-12 v4 BeadChip (Illumina) and HumanOmniExpress-12v1.0 BeadChip (Illumina). We tested 609,704 SNPs [minor allele frequency (MAF) > 0.04] and expression data for 15,421 probes for 414 individuals in the naïve state, 367 individuals after exposure to IFN-γ, 322 individuals after 24-hour LPS, and 261 individuals after 2-hour LPS. To allow comparison with naïve monocytes from the same individuals, expression data from untreated, incubated samples from a subset of 59 individuals were used to regress out expression changes attributable to incubation from the treated samples. Data across all four conditions were available from 228 individuals, permitting cross-treatment comparison. As anticipated, treatment
