High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 31826855.
- Also identified by DOI 10.1136/annrheumdis-2019-216227 and PMC identifier 7034364.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE). Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci. SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10<sup>-86</sup> and OR 7.48 (6.73 to 8.32), p=2.2×10<sup>-304</sup> for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10<sup>-5</sup>), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10<sup>-2</sup>), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10<sup>-5</sup>), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10<sup>-3</sup>), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10<sup>-2</sup>), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10<sup>-3</sup>), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10<sup>-2</sup>), anti-β<sub>2</sub>-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10<sup>-3</sup>) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10<sup>-2</sup>) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10<sup>-2</sup>), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10<sup>-2</sup>), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10<sup>-7</sup>), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10<sup>-3</sup>) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10<sup>-2</sup>) in high to low quartile comparison. A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.
Medical subject headings
- Genetic Predisposition to Disease
- Lupus Erythematosus, Systemic
- Lupus Nephritis
- Risk Assessment
- Severity of Illness Index