Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations

• DOI: 10.1038/s41467-017-00366-1
• Publication Date: 2017-08-08T15:59:52Z
• Authors: Sarah Kim-Hellmuth; Matthias Bechheim; Benno Pütz; Pejman Mohammadi; Yohann Nédélec; Nicholas Giangreco; Jessica Becker; Vera Kaiser; Nadine Fricker; Esther Beier; Peter Boor; Stephane E. Castel; Markus M. Nöthen; Luis B. Barreiro; Joseph K. Pickrell; Bertram Müller-My...; Tuuli Lappalainen; Johannes Schumacher; Veit Hornung
• Keywords: Genome-wide Association Study; Genetic predisposition

The immune system plays a major role in human health and disease, understanding genetic causes of interindividual variability responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, 5'-ppp-dsRNA), profile the transcriptomes at time points. Mapping expression quantitative trait loci (eQTL), identify 417 response eQTLs (reQTLs) varying effects between conditions. We characterize dynamics regulation on early late observe an enrichment reQTLs distal cis-regulatory elements. In addition, are enriched for recent positive selection evolutionary trend towards enhanced response. Finally, uncover reQTL multiple GWAS show stronger than constant signals several autoimmune diseases. This demonstrates importance infectious stimuli modifying predisposition to disease.Insight into influence important pathologies. authors generate transcriptome data blood stimulated various provide time-resolved eQTL map.