Clinical Perspectives on Lupus Genetics

In recent years, genome-wide association studies have led to an expansion in the identification of regions containing confirmed genetic risk variants within complex human diseases, such as systemic lupus erythematosus (SLE). Many of the strongest SLE genetic associations can be divided into groups based on their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination, DNA degradation, innate immunity, cellular immunity, lymphocyte development, and antigen presentation. Recent advances have also shown several genetic associations with SLE subphenotypes and subcriteria. Many areas for further exploration remain to move lupus genetic studies toward clinically informative end points.

Key points

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Polymorphisms in genes important for ubiquitination, DNA degradation, innate immunity, cellular immunity, antigen presentation, and lymphocyte development are associated and confirmed in systemic lupus erythematosus (SLE).
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Select genetic associations are enriched in patients with SLE with certain autoantibodies, antiphospholipid syndrome, pericarditis, thrombosis, arthritis, or lupus nephritis.
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New lupus genetic studies are warranted, especially with large cohorts enriched for understudied races, and in patients with severe disease or poor prognosis.
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New lupus genetic studies are also warranted in large cohorts of patients with SLE with phenotype information about common lupus comorbidities and response to therapeutics.