Systemic Lupus Erythematosus

  • Susan K. Vester
  • Timothy J. VyseEmail author
Part of the Rare Diseases of the Immune System book series (RDIS)


Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with a strong genetic component. Monogenic causes of SLE, such as complement deficiencies, are rare but have high penetrance and have been able to shed light on some disease-related pathways. However, in a majority of SLE cases, the genetics underlying this disease are complex and not fully explored. The advent of genome-wide association studies has led to the discovery of over 80 common variants robustly associated with SLE risk. However, missing heritability is still observed. Next-generation sequencing approaches such as targeted resequencing, whole-exome sequencing, or whole-genome sequencing have been harnessed in the search for rare variants, which may account for some of the missing heritability observed. High-penetrant rare variants are likely to lead the way in pinpointing pathways for therapeutic targeting. Both common and rare variants cannot, however, be viewed entirely independently, as modified penetrance of protein-coding variants through regulatory haplotypes, as well as common variant haplotypes, has been observed in SLE.


Systemic lupus erythematosus Missing heritability Common variants Rare variants De novo mutations Penetrance Haplotype 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medical and Molecular GeneticsKing’s College LondonLondonUK
  2. 2.Department of Medical and Molecular GeneticsKing’s College London, Guy’s HospitalLondonUK

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