The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis

Cell. 2015 Apr 9;161(2):387-403. doi: 10.1016/j.cell.2015.02.046. Epub 2015 Mar 12.


Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Aged
  • Autoimmune Diseases / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Immune System Diseases / genetics*
  • Immunophenotyping*
  • Leukocytes / cytology
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, IgG / genetics
  • T-Lymphocytes, Regulatory / cytology


  • Receptors, IgG