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

Raul Aguirre-Gamboa; Irma Joosten; Paulo C. M. Urbano; Renate G. van der Molen; Esther van Rijssen; Bram van Cranenbroek; Marije Oosting; Sanne Smeekens; Martin Jaeger; Maria Zorro; Sebo Withoff; Antonius E. van Herwaarden; Fred C. G. J. Sweep; Romana T. Netea; Morris A. Swertz; Lude Franke; Ramnik J. Xavier; Leo A. B. Joosten; Mihai G. Netea; Cisca Wijmenga; Vinod Kumar; Yang Li; Hans J. P. M. Koenen

doi:10.1016/j.celrep.2016.10.053

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

Raul Aguirre-Gamboa, Irma Joosten, Paulo C. M. Urbano, Renate G. van der Molen, Esther van Rijssen, Bram van Cranenbroek, Marije Oosting, Sanne Smeekens, Martin Jaeger, Maria Zorro, Sebo Withoff, Antonius E. van Herwaarden, Fred C. G. J. Sweep, Romana T. Netea, Morris A. Swertz, Lude Franke, Ramnik J. Xavier, Leo A. B. Joosten, Mihai G. Netea, Cisca WijmengaVinod Kumar, Yang Li, Hans J. P. M. Koenen

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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 similar to 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.

Original language	English
Pages (from-to)	2474-2487
Number of pages	14
Journal	Cell reports
Volume	17
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2016.10.053
Publication status	Published - 22-Nov-2016

Keywords

GENOME-WIDE ASSOCIATION
IMMUNOGLOBULIN PRODUCTION
EXPRESSION ANALYSIS
CYTOKINE PRODUCTION
INNATE IMMUNITY
SYSTEM
AGE
DISEASE
HUMANS
HERITABILITY

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Aguirre-Gamboa, R., Joosten, I., Urbano, P. C. M., van der Molen, R. G., van Rijssen, E., van Cranenbroek, B., Oosting, M., Smeekens, S., Jaeger, M., Zorro, M., Withoff, S., van Herwaarden, A. E., Sweep, F. C. G. J., Netea, R. T., Swertz, M. A., Franke, L., Xavier, R. J., Joosten, L. A. B., Netea, M. G., ... Koenen, H. J. P. M. (2016). Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits. Cell reports, 17(9), 2474-2487. https://doi.org/10.1016/j.celrep.2016.10.053

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title = "Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits",

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 similar to 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.",

keywords = "GENOME-WIDE ASSOCIATION, IMMUNOGLOBULIN PRODUCTION, EXPRESSION ANALYSIS, CYTOKINE PRODUCTION, INNATE IMMUNITY, SYSTEM, AGE, DISEASE, HUMANS, HERITABILITY",

author = "Raul Aguirre-Gamboa and Irma Joosten and Urbano, {Paulo C. M.} and {van der Molen}, {Renate G.} and {van Rijssen}, Esther and {van Cranenbroek}, Bram and Marije Oosting and Sanne Smeekens and Martin Jaeger and Maria Zorro and Sebo Withoff and {van Herwaarden}, {Antonius E.} and Sweep, {Fred C. G. J.} and Netea, {Romana T.} and Swertz, {Morris A.} and Lude Franke and Xavier, {Ramnik J.} and Joosten, {Leo A. B.} and Netea, {Mihai G.} and Cisca Wijmenga and Vinod Kumar and Yang Li and Koenen, {Hans J. P. M.}",

year = "2016",

month = nov,

day = "22",

doi = "10.1016/j.celrep.2016.10.053",

language = "English",

volume = "17",

pages = "2474--2487",

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Aguirre-Gamboa, R, Joosten, I, Urbano, PCM, van der Molen, RG, van Rijssen, E, van Cranenbroek, B, Oosting, M, Smeekens, S, Jaeger, M, Zorro, M, Withoff, S, van Herwaarden, AE, Sweep, FCGJ, Netea, RT, Swertz, MA , Franke, L, Xavier, RJ, Joosten, LAB, Netea, MG, Wijmenga, C , Kumar, V , Li, Y & Koenen, HJPM 2016, 'Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits', Cell reports, vol. 17, no. 9, pp. 2474-2487. https://doi.org/10.1016/j.celrep.2016.10.053

TY - JOUR

T1 - Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

AU - Aguirre-Gamboa, Raul

AU - Joosten, Irma

AU - Urbano, Paulo C. M.

AU - van der Molen, Renate G.

AU - van Rijssen, Esther

AU - van Cranenbroek, Bram

AU - Oosting, Marije

AU - Smeekens, Sanne

AU - Jaeger, Martin

AU - Zorro, Maria

AU - Withoff, Sebo

AU - van Herwaarden, Antonius E.

AU - Sweep, Fred C. G. J.

AU - Netea, Romana T.

AU - Swertz, Morris A.

AU - Franke, Lude

AU - Xavier, Ramnik J.

AU - Joosten, Leo A. B.

AU - Netea, Mihai G.

AU - Wijmenga, Cisca

AU - Kumar, Vinod

AU - Li, Yang

AU - Koenen, Hans J. P. M.

PY - 2016/11/22

Y1 - 2016/11/22

N2 - 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 similar to 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.

AB - 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 similar to 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.

KW - GENOME-WIDE ASSOCIATION

KW - IMMUNOGLOBULIN PRODUCTION

KW - EXPRESSION ANALYSIS

KW - CYTOKINE PRODUCTION

KW - INNATE IMMUNITY

KW - SYSTEM

KW - AGE

KW - DISEASE

KW - HUMANS

KW - HERITABILITY

U2 - 10.1016/j.celrep.2016.10.053

DO - 10.1016/j.celrep.2016.10.053

M3 - Article

C2 - 27818087

VL - 17

SP - 2474

EP - 2487

JO - Cell reports

JF - Cell reports

SN - 2211-1247

IS - 9

ER -