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Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors

Patin, Etienne ; Hasan, Milena ; Bergstedt, Jacob LU ; Rouilly, Vincent ; Libri, Valentina ; Urrutia, Alejandra ; Alanio, Cécile ; Scepanovic, Petar ; Hammer, Christian and Jönsson, Friederike , et al. (2018) In Nature Immunology 19. p.302-314
Abstract
The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated... (More)
The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases. (Less)
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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Immunology
volume
19
pages
302 - 314
publisher
Nature Publishing Group
external identifiers
  • scopus:85042410142
  • pmid:29476184
ISSN
1529-2908
DOI
10.1038/s41590-018-0049-7
language
English
LU publication?
yes
id
856ab6b2-b1f1-40a6-aa60-1f2d51d455cf
date added to LUP
2018-02-26 14:41:38
date last changed
2022-08-23 11:05:02
@article{856ab6b2-b1f1-40a6-aa60-1f2d51d455cf,
  abstract     = {{The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.}},
  author       = {{Patin, Etienne and Hasan, Milena and Bergstedt, Jacob and Rouilly, Vincent and Libri, Valentina and Urrutia, Alejandra and Alanio, Cécile and Scepanovic, Petar and Hammer, Christian and Jönsson, Friederike and Beitz, Benoît and Quach, Helene and Lim, Yoong Wearn and Hunkapiller, Julie and Zepeda, Magge and Green, Cherie and Piasecka, Barbara and Leloup, Claire and Rogge, Lars and Huetz, François and Peguillet, Isabelle and Lantz, Olivier and Fontes, Magnus and Santo, James P. and Thomas, Stéphanie and Fellay, Jacques and Duffy, Darragh and Quintana-Murci, Lluis and Albert, Matthew L}},
  issn         = {{1529-2908}},
  language     = {{eng}},
  month        = {{02}},
  pages        = {{302--314}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Immunology}},
  title        = {{Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors}},
  url          = {{http://dx.doi.org/10.1038/s41590-018-0049-7}},
  doi          = {{10.1038/s41590-018-0049-7}},
  volume       = {{19}},
  year         = {{2018}},
}