Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

Cell Rep. 2016 Nov 22;17(9):2474-2487. doi: 10.1016/j.celrep.2016.10.053. Epub 2016 Nov 3.


Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell populations in peripheral blood, including associations with immunoglobulin concentrations, from ∼500 healthy volunteers from the Human Functional Genomics Project. Genetic heritability estimation showed that variations in T cell numbers are more strongly driven by genetic factors, while B cell counts are more environmentally influenced. Quantitative trait loci (QTL) mapping identified eight independent genomic loci associated with leukocyte count variation, including four associations with T and B cell subtypes. The QTLs identified were enriched among genome-wide association study (GWAS) SNPs reported to increase susceptibility to immune-mediated diseases. Our systems approach provides insights into cellular and humoral immune trait variability in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • B-Lymphocytes / immunology*
  • Chromosomes, Human / genetics
  • Cohort Studies
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • Environment*
  • Female
  • Humans
  • Immunity, Cellular / genetics*
  • Immunity, Humoral / genetics*
  • Immunoglobulins / metabolism
  • Lymphocyte Count
  • Lymphocyte Subsets / metabolism
  • Male
  • Middle Aged
  • Myosin Type I / genetics
  • Netherlands
  • Quantitative Trait Loci / genetics
  • Seasons
  • T-Lymphocytes / immunology*
  • Young Adult


  • Immunoglobulins
  • MYO1B protein, human
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4A protein, human
  • Myosin Type I