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Chunk #2 — Results — Identifying Context-Specific Local Genetic Regulatory Variants

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Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.
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Local, likely cis-acting eQTL (referred to as cis-eQTL) were defined as SNPs showing association with gene expression that were located within a 1-Mb window of the associated probe. We tested for association with gene expression using an additive linear model (18). We included surrogate variables consisting of major principal components (PC) of the expression data as covariates to limit the effect of confounding factors. Similar to others (19, 20), we find this enhanced detection of cis- and trans-eQTLs (fig. S2). Using this approach, we found that the majority of all cis-eQTLs observed affected gene expression only upon cell stimulation, and a significant proportion of constitutive eQTL present in naïve cells were no longer present after treatment (Fig. 1, A and B, and table S2). Across all four data sets, most genes show evidence of eQTL, with 83.7% of probes tested (12,905/15,421 probes) showing association under at least one condition [false discovery rate (FDR) < 0.05].