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Cell Rep. 2016 Nov 22;17(9):2474-2487. doi: 10.1016/j.celrep.2016.10.053. Epub 2016 Nov 3.

Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits.

Author information

1
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
2
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
3
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
4
Department of Laboratory Medicine, Laboratory for Clinical Chemistry, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
5
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands; Genomics Coordination Center, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
6
Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital and Harvard School of Medicine, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
7
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands; Department of Immunology, Oslo University Hospital, University of Oslo, Rikshospitalet, 0372 Oslo Norway.
8
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands. Electronic address: y.li01@umcg.nl.
9
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands. Electronic address: hans.koenen@radboudumc.nl.

Abstract

Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell populations in peripheral blood, including associations with immunoglobulin concentrations, from ∼500 healthy volunteers from the Human Functional Genomics Project. Genetic heritability estimation showed that variations in T cell numbers are more strongly driven by genetic factors, while B cell counts are more environmentally influenced. Quantitative trait loci (QTL) mapping identified eight independent genomic loci associated with leukocyte count variation, including four associations with T and B cell subtypes. The QTLs identified were enriched among genome-wide association study (GWAS) SNPs reported to increase susceptibility to immune-mediated diseases. Our systems approach provides insights into cellular and humoral immune trait variability in humans.

PMID:
27818087
PMCID:
PMC5130901
DOI:
10.1016/j.celrep.2016.10.053
[Indexed for MEDLINE]
Free PMC Article

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