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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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@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 and , },
  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},
  volume       = {19},
  year         = {2018},
}