Authors
Yang Li, Marije Oosting, Sanne P Smeekens, Martin Jaeger, Raul Aguirre-Gamboa, Kieu TT Le, Patrick Deelen, Isis Ricaño-Ponce, Teske Schoffelen, Anne FM Jansen, Morris A Swertz, Sebo Withoff, Esther van de Vosse, Marcel van Deuren, Frank van de Veerdonk, Alexandra Zhernakova, Jos WM van der Meer, Ramnik J Xavier, Lude Franke, Leo AB Joosten, Cisca Wijmenga, Vinod Kumar, Mihai G Netea
Publication date
2016/11/3
Journal
Cell
Volume
167
Issue
4
Pages
1099-1110. e14
Publisher
Cell Press
Description
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 …
Scholar articles
Y Li, M Oosting, SP Smeekens, M Jaeger… - Cell, 2016