Included in eqtl, systemic_lupus_erythematosus themes

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Research area: genomics

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Identification of drug eQTL interactions from repeat transcriptional and environmental measurements in a lupus clinical trial

Created on 20th March 2017

Emma Elisabeth Davenport; Tiffany Amariuta; Maria Gutierrez-Arcelus; Kamil Slowikowski; Harm-Jan Westra; Ying Zhang; Stephen Pearson; David von Schack; Jean S. Beebe; Nan Bing; Michael S. Vincent; Baohong Zhang; Soumya Raychaudhuri;

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<0.001). IFN interactions are enriched for IRF1 motifs, and 91/126 drug-eQTL interactions are consistent with interactions using free IL-6 protein levels. This same approach can be easily used to define informative drug exposure scores, and can be applied to larger drug trials to further our understanding of the drug mechanisms.

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