Kim-Hellmuth, Sarah, Bechheim, Matthias, Puetz, Benno, Mohammadi, Pejman, Nedelec, Yohann, Giangreco, Nicholas, Becker, Jessica, Kaiser, Vera, Fricker, Nadine, Beier, Esther et al (show 9 more authors)
(2017)
Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations.
NATURE COMMUNICATIONS, 8 (1).
266-.
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Genetic regulatory effects modified by immune activation contribute to autoimmune disease associations.pdf - Published version Download (1MB) |
Abstract
The immune system plays a major role in human health and disease, and understanding genetic causes of interindividual variability of immune responses is vital. Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5′-ppp-dsRNA), and profile the transcriptomes at three time points. Mapping expression quantitative trait loci (eQTL), we identify 417 response eQTLs (reQTLs) with varying effects between conditions. We characterize the dynamics of genetic regulation on early and late immune response and observe an enrichment of reQTLs in distal cis-regulatory elements. In addition, reQTLs are enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover reQTL effects in multiple GWAS loci and show a stronger enrichment for response than constant eQTLs in GWAS signals of several autoimmune diseases. This demonstrates the importance of infectious stimuli in modifying genetic predisposition to disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Monocytes, Humans, Autoimmune Diseases, Genetic Predisposition to Disease, Acetylmuramyl-Alanyl-Isoglutamine, Lipopolysaccharides, Lipids, RNA, Double-Stranded, RNA, Messenger, Adjuvants, Immunologic, Indicators and Reagents, Gene Expression Profiling, Gene Expression, Gene Expression Regulation, Regulatory Sequences, Nucleic Acid, Quantitative Trait Loci, Adolescent, Adult, Male, Young Adult, Healthy Volunteers |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Sep 2017 06:44 |
| Last Modified: | 19 Jan 2023 06:54 |
| DOI: | 10.1038/s41467-017-00366-1 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3009488 |
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