Genetic susceptibility to SLE: recent progress from GWAS

J Autoimmun. 2013 Mar;41:25-33. doi: 10.1016/j.jaut.2013.01.008. Epub 2013 Feb 6.


Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component, characterized by hyperactive T and B cells, autoantibody production, immune complex deposition and multi-organ damage. It affects predominantly women of child-bearing age and has population differences in both disease prevalence and severity. Genetic factors are known to play key roles in the disease through the use of association and family studies. Previously, SLE susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Since 2008, our understanding of the genetic basis of SLE has been rapidly advanced through genome-wide association studies (GWASs). More than 40 robust susceptibility loci have been identified and conformed to be associated with SLE using this technique. Most of these associated genes productions participate in important pathways involved in the pathogenesis of SLE, such as immune complex processing, toll-like receptor signaling, type I interferon production, and so on. A number of susceptibility loci with unknown functions in the pathogenesis of SLE have also been identified, indicating that additional molecular mechanisms contribute to the risk of developing SLE. It is noteworthy that susceptibility loci of SLE are shared by other immune-related diseases. Thus, common molecular pathways may be involved in the pathogenesis of these diseases. In this review, we summarize the key loci, achieving genome-wide significance, which have been shown to predispose to SLE. Analysis of relevant molecular pathways suggests new etiologic clues to SLE development. These genetic loci may help building the foundation for genetic diagnosis and personalized treatment for patients with SLE in the near future. However, substantial additional studies, including functional and gene-targeted studies, are required to confirm the causality of the genetic variants and their biological relevance in SLE development.

Publication types

  • Review

MeSH terms

  • Genetic Predisposition to Disease*
  • Genome, Human / genetics*
  • Genome-Wide Association Study / methods*
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Polymorphism, Single Nucleotide
  • Signal Transduction / genetics
  • Toll-Like Receptors / genetics


  • Toll-Like Receptors