TY - JOUR T1 - Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations JF - bioRxiv DO - 10.1101/116376 SP - 116376 AU - Sarah Kim-Hellmuth AU - Matthias Bechheim AU - Benno Pütz AU - Pejman Mohammadi AU - Yohann Nédélec AU - Nicholas Giangreco AU - Jessica Becker AU - Vera Kaiser AU - Nadine Fricker AU - Esther Beier AU - Peter Boor AU - Stephane Castel AU - Markus M. Nöthen AU - Luis B. Barreiro AU - Joseph K. Pickrell AU - Bertram Müller-Myhsok AU - Tuuli Lappalainen AU - Johannes Schumacher AU - Veit Hornung Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/13/116376.abstract N2 - The immune system plays a major role in human health and disease, and understanding genetic causes of interindividual variability of immune responses is vital. We isolated monocytes from 134 genotyped individuals, stimulated the cells with three defined microbe-associated molecular patterns (LPS, MDP, and ppp-dsRNA), and profiled the transcriptome at three time points. After mapping expression quantitative trait loci (eQTL), we identified 417 response eQTLs (reQTLs) with differing effect between the conditions. We characterized the dynamics of genetic regulation on early and late immune response, and observed an enrichment of reQTLs in distal cis-regulatory elements. Response eQTLs are also enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover novel reQTL effects in multiple GWAS loci, and show a stronger enrichment of response than constant eQTLs in GWAS signals of several autoimmune diseases. This demonstrates the importance of infectious stimuli modifying genetic predisposition to disease. ER -