Genetics, environment, and gene-environment interactions in the development of systemic rheumatic diseases

Rheum Dis Clin North Am. 2014 Nov;40(4):637-57. doi: 10.1016/j.rdc.2014.07.005. Epub 2014 Sep 2.


Rheumatic diseases offer distinct challenges to researchers because of heterogeneity in disease phenotypes, low disease incidence, and geographic variation in genetic and environmental factors. Emerging research areas, including epigenetics, metabolomics, and the microbiome, may provide additional links between genetic and environmental risk factors in the pathogenesis of rheumatic disease. This article reviews the methods used to establish genetic and environmental risk factors and studies gene-environment interactions in rheumatic diseases, and provides specific examples of successes and challenges in identifying gene-environment interactions in rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Emerging research strategies and future challenges are discussed.

Keywords: Ankylosing spondylitis; Environment; Genetics; Interaction; Rheumatoid arthritis; Smoking; Systemic lupus erythematosus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics
  • Environmental Exposure / statistics & numerical data*
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease
  • HLA-B27 Antigen / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Intestines / microbiology
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / genetics
  • Rheumatic Diseases / epidemiology
  • Rheumatic Diseases / genetics*
  • Risk Factors
  • Smoking / epidemiology
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / microbiology
  • Ultraviolet Rays


  • HLA-B27 Antigen
  • HLA-DRB1 Chains