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

Nature Immunology
Etienne PatinMilieu Intérieur Consortium

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.

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Datasets Mentioned

BETA
EGAS00001002460

Methods Mentioned

BETA
flow cytometry
flow-cytometry
flow
genotyping
FCS
blood draw
PCA

Clinical Trials Mentioned

NCT01699893

Software Mentioned

EIGENSTRAT
pbkrtest R
missForest
R package
LASSO
GEMMA
relaimpo R package
ComBat
GenABEL
lme4 R

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