Novel Shared Genetic Risk Locus Identified for RA and SLE

Personalized Medicine and Genetic Testing to Predict Treatment Response
Personalized Medicine and Genetic Testing to Predict Treatment Response
A shared genetic locus (COG6) increased the risk for both systemic lupus erythematosus and rheumatoid arthritis.

A novel shared risk locus for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) has been identified by a research team led by Dr Ana Márquez of the Instituto de Parasitología y Biomedicina López-Neyra in Granada, Spain.1 These results were recently published in Annals of the Rheumatic Diseases.

Dr Márquez and her colleagues performed a large-scale meta-analysis of genome-wide association studies (GWAS) data from RA (3911 cases and 4083 controls) and SLE (2237 cases and 6315 controls). GWAS employs microarray technology and statistical analysis to compare the DNA of different individuals in order to determine which common genetic variants are associated with a given trait or disease.2 

While more limited studies had previously explored the overlap between several known risk loci for SLE and RA, this study was the first comprehensive large-scale genetic analysis undertaken to determine the genetic overlap between the two diseases. Both diseases were considered as a single phenotype for the purposes of the analysis. 

“A main advantage of combining GWAS data from related diseases is to increase the statistical power in order to capture association signals that may have been undetected in previous disease-specific studies,” wrote the investigators. The investigators used PLINK V.1.07, an open-source whole GWAS toolset, to perform the analysis.

High Yield Data Summary

  • A shared genetic locus (COG6) increased the susceptibility risk for both SLE and RA 
  • Reclassifying patients according to genetic risk may help guide treatment in the future

The polymorphism which achieved genome-wide significance in the combined analysis was the rs9603612 variant, located close to the component of oligomeric Golgi complex 6 (COG6) gene. 

COG6 is a subunit of the Golgi apparatus, a peripheral membrane protein complex that helps to organize protein sorting and glycosylation in the cell. COG6 had already been established as a susceptibility locus for RA and psoriasis. 

The authors stated that while researchers have previously speculated about the possible implication of COG6 in autoimmunity, the exact role that it plays in immune-mediated disorders has not yet been determined. 

“It has been described that deficiency of this gene may lead to a clinical phenotype including inflammatory bowel disease and neutrophil and B and T-cell dysfunction,” they noted.

Summary and Clinical Applicability

Dr Márquez and colleagues concluded that COG6 should be added to the list of risk factors known to be shared in RA and SLE. 

“Our results highlight the existence of a relevant genetic correlation between both diseases as well as the influence of common molecular mechanisms in their pathophysiology,” they stated. 

The common genetic pathways between RA and SLE that have been implicated in this study may pave the way for reclassifying patients by genetics for tailored therapy. 

Limitations and Disclosures

Low single nucleotide polymorphism coverage could have accounted for the lack of association signals within AFF3.

No competing interests were declared by the researchers.


1.     Márquez A, Vidal-Bralo L, Rodríguez-Rodríguez L, et al. A combined large-scale meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis.  Epub ahead of print May 18, 2016. doi:10.1136/annrheumdis-2016-209436

2.     Li DW. Genome-Wide Association Study. In: Dubitzky W, Wolkenhauer O, Cho K-H, Yokota H, eds. Encyclopedia of Systems Biology. Springer New York; 2013:834-834. 

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