期刊
CELL
卷 167, 期 4, 页码 1099-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.10.017
关键词
-
资金
- ERC Consolidator grant [3310372]
- IN-CONTROL CVON grant [CVON2012-03]
- Spinoza prize [NWO SPI 94-212, NWO SPI 92266]
- ERC advanced grant (FP7/ERC grant) [2012-322698]
- Dutch Digestive Diseases Foundation grant [MLDS WO11-30]
- European Union Seventh Framework Programme grant (EU FP7) TANDEM project [HEALTH-F3-2012-305279]
- Netherlands Organization for Scientific Research (NWO) VENI grant [863.13.011]
- BBMRI-NL
- Netherlands Organization for Scientific Research (NWO) [184.021.007]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据