Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
Etienne Patin, Milena Hasan, Jacob Bergstedt, Vincent Rouilly, Valentina Libri, Alejandra Urrutia, Cécile Alanio, Petar Scepanovic, Christian Hammer, Friederike Jönsson, Benoît Beitz, Hélène Quach, Yoong Wearn Lim, Julie Hunkapiller, Magge Zepeda, Cherie Green, Barbara Piasecka, Claire Leloup, Lars Rogge, François Huetz, Isabelle Peguillet, Olivier Lantz, Magnus Fontes, James P Di Santo, Stéphanie Thomas, Jacques Fellay, Darragh Duffy, Lluís Quintana-Murci, Matthew L Albert, Milieu Intérieur Consortium, Laurent Abel, Andres Alcover, Kalle Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James P Di Santo, Françoise Dromer, Darragh Duffy, Gérard Eberl, Jost Enninga, Jacques Fellay, Antonio Freitas, Odile Gelpi, Ivo Gomperts Boneca, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Marie-Noëlle Ungeheuer, Lluís Quintana-Murci, Matthew L Albert, Etienne Patin, Milena Hasan, Jacob Bergstedt, Vincent Rouilly, Valentina Libri, Alejandra Urrutia, Cécile Alanio, Petar Scepanovic, Christian Hammer, Friederike Jönsson, Benoît Beitz, Hélène Quach, Yoong Wearn Lim, Julie Hunkapiller, Magge Zepeda, Cherie Green, Barbara Piasecka, Claire Leloup, Lars Rogge, François Huetz, Isabelle Peguillet, Olivier Lantz, Magnus Fontes, James P Di Santo, Stéphanie Thomas, Jacques Fellay, Darragh Duffy, Lluís Quintana-Murci, Matthew L Albert, Milieu Intérieur Consortium, Laurent Abel, Andres Alcover, Kalle Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James P Di Santo, Françoise Dromer, Darragh Duffy, Gérard Eberl, Jost Enninga, Jacques Fellay, Antonio Freitas, Odile Gelpi, Ivo Gomperts Boneca, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Marie-Noëlle Ungeheuer, Lluís Quintana-Murci, Matthew L Albert
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.
Source: PubMed