Identification of drug eQTL interactions from repeat transcriptional and environmental measurements in a lupus clinical trial
2017
We hypothesize that regulatory mechanisms influenced by an environmental perturbagen may be identified with eQTL (expression quantitative trait locus) interactions, which alter the relationship between a genetic variant and transcript levels. In an anti-IL-6 clinical trial of 157 patients with systemic lupus erythematosus (SLE) we measured cell counts, interferon (IFN) signature, and drug exposure at three time points alongside genome-wide transcription. Repeated transcriptomic measurements detected 4,976 cis eQTLs, 63% more than detectable from single measurements. We identified 154, 185 and 126 nominal eQTL interactions with T cell count, IFN status and anti-IL-6 drug exposure respectively (more than expected by chance, p
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