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17-12-2019 | Systemic lupus erythematosus | Highlight | News

Cumulative genetic risk score predicts SLE outcomes

medwireNews: People with a high genetic risk score (GRS) for systemic lupus erythematosus (SLE) experience earlier disease onset, as well as higher rates of complications and mortality, than those with a low score, researchers report.

Lars Rönnblom (Uppsala University, Sweden) and co-investigators therefore believe their findings “indicate that genetic profiling may provide a tool for predicting disease outcome and thus aid in the clinical decision process” for patients with SLE.

The study included a discovery cohort of 1001 patients who fulfilled at least four ACR-82 classification criteria for SLE and 2802 healthy controls.

Both the patients and controls underwent genotyping using the Illumina 200K Immunochip SNP array (SNP&SEQ Technology Platform, Science for Life Laboratory, Uppsala) and were assigned an individual GRS based on 57 single nucleotide polymorphisms that had previously been associated with SLE at a genome wide significance level in the European population.

Rönnblom and team found that the prevalence of SLE rose significantly with increasing GRS, such that individuals in the highest GRS quartile were 12.32 times more likely to have the condition than those in the lowest quartile.

Furthermore, individuals in the highest GRS quartile were diagnosed with SLE at a significantly younger age than those in the lowest quartile, at 33 versus 39 years.

The GRS was also associated with the prevalence of organ damage, as defined by the SLICC Damage Index. In this case, damage accrual was a significant 1.47 times more common in the high versus low GRS cohorts, with individuals in the former group acquiring their first damage at a mean 43 years of age compared with 51 years in the latter group.

Similar patterns were seen for cardiovascular events (mean age at first event of 45 vs 51 years for top vs bottom GRS quartile), nephritis (31 vs 39 years), and end-stage renal disease (ESRD; 43 vs 64 years).

In addition, the risk for mortality increased a significant 1.83-fold for people in the highest versus the lowest GRS quartile.

Other clinical and serologic manifestations that were significantly more common in the high versus low GRS quartiles included anti-dsDNA, anti-cardiolipin-IgG, anti-β2-glycoprotein-I-IgG, and positive test for lupus anticoagulant, as well as immunologic and renal disorders.

Data from a replication cohort of 5525 SLE patients and 9859 controls also showed that the likelihood of SLE was significantly higher with a top-quartile GRS than with a bottom-quartile GRS, at an odds ratio of 7.48.

Writing in the Annals of the Rheumatic Diseases, the researchers conclude: “Our study is the first to demonstrate an association between high cumulative genetic risk and survival, organ damage, cardiovascular disease, proliferative nephritis, ESRD and antiphospholipid antibodies in patients with SLE, introducing GRSs as a potential tool for prediction of disease severity.”

By Laura Cowen


Ann Rheum Dis 2019; doi:10.1136/annrheumdis-2019-216227

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