Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations
作者： Sarah Kim-Hellmuth , Matthias Bechheim , Benno Pütz , Pejman Mohammadi , Yohann Nédélec
DOI: 10.1101/116376
关键词: Genome-wide association study 、 Expression quantitative trait loci 、 Autoimmune disease 、 Genetics 、 RNA silencing 、 Transcriptome 、 Immune system 、 Genetic predisposition 、 Biology 、 Disease
摘要: The immune system plays a major role in human health and disease, understanding genetic causes of interindividual variability responses is vital. We isolated monocytes from 134 genotyped individuals, stimulated the cells with three defined microbe-associated molecular patterns (LPS, MDP, ppp- dsRNA), profiled transcriptome at time points. After mapping expression quantitative trait loci (eQTL), we identified 417 response eQTLs (reQTLs) differing effect between conditions. characterized dynamics regulation on early late response, observed an enrichment reQTLs distal cis-regulatory elements. Response are also enriched for recent positive selection evolutionary trend towards enhanced response. Finally, uncover novel reQTL effects multiple GWAS loci, show stronger than constant signals several autoimmune diseases. This demonstrates importance infectious stimuli modifying predisposition to disease.
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