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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Etienne Patin
  • Milena Hasan
  • Jacob Bergstedt
  • Vincent Rouilly
  • Valentina Libri
  • Alejandra Urrutia
  • Cécile Alanio
  • Petar Scepanovic
  • Christian Hammer
  • Friederike Jönsson
  • Benoît Beitz
  • Helene 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. Santo
  • Stéphanie Thomas
  • Jacques Fellay
  • Darragh Duffy
  • Lluis Quintana-Murci
  • Matthew L Albert
  • The Milieu Intérieur Consortium
Organisations
External organisations
  • Pasteur Institute
  • Genentech, Inc
  • Swiss Federal Institute of Technology
  • Paris Descartes University
  • Curie Institute, Paris
  • Swiss Institute of Bioinformatics
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)302–314
JournalNature Immunology
Volume19
Publication statusPublished - 2018 Feb 23
Publication categoryResearch
Peer-reviewedYes