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

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 p...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2016-11, Vol.17 (9), p.2474-2487
Main Authors: Aguirre-Gamboa, Raul, Joosten, Irma, Urbano, Paulo C.M., van der Molen, Renate G., van Rijssen, Esther, van Cranenbroek, Bram, Oosting, Marije, Smeekens, Sanne, Jaeger, Martin, Zorro, Maria, Withoff, Sebo, van Herwaarden, Antonius E., Sweep, Fred C.G.J., Netea, Romana T., Swertz, Morris A., Franke, Lude, Xavier, Ramnik J., Joosten, Leo A.B., Netea, Mihai G., Wijmenga, Cisca, Kumar, Vinod, Li, Yang, Koenen, Hans J.P.M.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age Factors
Aged
B-Lymphocytes - immunology
Chromosomes, Human - genetics
Cohort Studies
Cyclic Nucleotide Phosphodiesterases, Type 4 - genetics
Environment
Female
Humans
Immunity, Cellular - genetics
Immunity, Humoral - genetics
Immunoglobulins - metabolism
Lymphocyte Count
Lymphocyte Subsets - metabolism
Male
Middle Aged
Myosin Type I - genetics
Netherlands
Quantitative Trait Loci - genetics
Resource
Seasons
T-Lymphocytes - immunology
Young Adult
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Summary: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. [Display omitted] •Understanding inter-individual variation of immune cells and immunoglobulin levels•Season and gender influence B cell subpopulation abundance•Identification of genetic loci that might regulate B cell levels in blood•Cell count QTLs overlap with risk SNPs for (auto)immune/inflammatory disease As part of the Human Functional Genomics Project, this study by Aguirre-Gamboa et al. maps the contribution of genetics and non-heritable factors onto immune-cell counts and immunoglobulin levels. They find that season and gender influence the abundance of most of B cell subpopulations.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2016.10.053