Recent advances in the genetics of autoimmune disease

Annu Rev Immunol. 2009:27:363-91. doi: 10.1146/annurev.immunol.021908.132653.

Abstract

Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmunity / genetics*
  • Autoimmunity / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / immunology
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • BANK1 protein, human
  • Cytokines
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Pattern Recognition
  • Receptors, Tumor Necrosis Factor
  • Transcription Factors
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22