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 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.
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
Raul
R
Aguirre-Gamboa
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Irma
I
Joosten
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Paulo C M
PCM
Urbano
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Renate G
RG
van der Molen
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Esther
E
van Rijssen
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Bram
B
van Cranenbroek
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Marije
M
Oosting
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Sanne
S
Smeekens
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Martin
M
Jaeger
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
Maria
M
Zorro
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
Sebo
S
Withoff
Department of Laboratory Medicine, Laboratory for Clinical Chemistry, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Antonius E
AE
van Herwaarden
Department of Laboratory Medicine, Laboratory for Clinical Chemistry, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Fred C G J
FCGJ
Sweep
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Romana T
RT
Netea
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.
Morris A
MA
Swertz
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
Lude
L
Franke
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.
Ramnik J
RJ
Xavier
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Leo A B
LAB
Joosten
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Mihai G
MG
Netea
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.
Cisca
C
Wijmenga
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands.
Vinod
V
Kumar
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands. Electronic address: y.li01@umcg.nl.
Yang
Y
Li
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands. Electronic address: hans.koenen@radboudumc.nl.
Hans J P M
HJPM
Koenen
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D002877:Chromosomes, Human / Q000235:genetics; D015331:Cohort Studies; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics; D004777:Environment; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D056724:Immunity, Humoral / Q000235:genetics*; D007136:Immunoglobulins / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D024461:Myosin Type I / Q000235:genetics; D009426:Netherlands; D040641:Quantitative Trait Loci / Q000235:genetics; D012621:Seasons; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
D007136:Immunoglobulins; C000594736:MYO1B protein, human; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517355:PDE4A protein, human; D024461:Myosin Type I