| Literature DB >> 27814507 |
Yang Li1, Marije Oosting2, Sanne P Smeekens2, Martin Jaeger2, Raul Aguirre-Gamboa3, Kieu T T Le3, Patrick Deelen4, Isis Ricaño-Ponce3, Teske Schoffelen2, Anne F M Jansen2, Morris A Swertz4, Sebo Withoff3, Esther van de Vosse5, Marcel van Deuren2, Frank van de Veerdonk2, Alexandra Zhernakova3, Jos W M van der Meer2, Ramnik J Xavier6, Lude Franke3, Leo A B Joosten7, Cisca Wijmenga8, Vinod Kumar9, Mihai G Netea10.
Abstract
As part of the Human Functional Genomics Project, which aims to understand the factors that determine the variability of immune responses, we investigated genetic variants affecting cytokine production in response to ex vivo stimulation in two independent cohorts of 500 and 200 healthy individuals. We demonstrate a strong impact of genetic heritability on cytokine production capacity after challenge with bacterial, fungal, viral, and non-microbial stimuli. In addition to 17 novel genome-wide significant cytokine QTLs (cQTLs), our study provides a comprehensive picture of the genetic variants that influence six different cytokines in whole blood, blood mononuclear cells, and macrophages. Important biological pathways that contain cytokine QTLs map to pattern recognition receptors (TLR1-6-10 cluster), cytokine and complement inhibitors, and the kallikrein system. The cytokine QTLs show enrichment for monocyte-specific enhancers, are more often located in regions under positive selection, and are significantly enriched among SNPs associated with infections and immune-mediated diseases. PAPERCLIP.Entities:
Keywords: cytokine QTL; cytokine heritability; immunogenomics; innate immune response
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Year: 2016 PMID： 27814507 DOI： 10.1016/j.cell.2016.10.017
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582