@article {Davenport118703, author = {Emma E. Davenport and Tiffany Amariuta and Maria Gutierrez-Arcelus and Kamil Slowikowski and Harm-Jan Westra and Ying Zhang and Stephen Pearson and David von Schack and Jean S. Beebe and Nan Bing and Michael S. Vincent and Baohong Zhang and Soumya Raychaudhuri}, title = {Discovering in vivo eQTL interactions with interferon status and drug exposure from a lupus clinical trial}, elocation-id = {118703}, year = {2017}, doi = {10.1101/118703}, publisher = {Cold Spring Harbor Laboratory}, abstract = {If an expression quantitative trait locus (eQTL) effect is modulated by an environmental stimulus, such as drug exposure or disease status, it can point to key regulatory mediators. In a clinical trial for anti-IL-6 in 157 patients with systemic lupus erythematosus we measured cell counts, interferon (IFN) status, drug exposure and genome-wide gene expression at three time points. First, we confirmed an increase in power using repeat transcriptomic measurements. Then, after detecting 4,976 cis eQTLs, we discovered that 154, 185 and 126 had evidence of significant eQTL interactions with T cell proportion, IFN status and anti-IL-6 drug exposure respectively. Next, we found an enrichment of transcription factor binding motifs interrupted by eQTL interaction SNPs, pointing to regulatory mediators of these environmental stimuli and therefore potential therapeutic targets for autoimmune diseases. In particular, IFN interactions are enriched for IRF1 binding site motifs, while anti-IL-6 interactions are enriched for IRF4 motifs. Finally, we used the drug-eQTL interactions to define an informative drug exposure score, reflecting a drug{\textquoteright}s effect in an individual patient, thus highlighting the potential for utilizing drug-eQTL interactions in a pharmacogenetic framework.}, URL = {https://www.biorxiv.org/content/early/2017/06/27/118703}, eprint = {https://www.biorxiv.org/content/early/2017/06/27/118703.full.pdf}, journal = {bioRxiv} }