High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus. Issue 3 (11th December 2019)

• Record Type: Journal Article
• Authors: Reid, Sarah; Alexsson, Andrei; Frodlund, Martina; Morris, David; Sandling, Johanna K; Bolin, Karin; Svenungsson, Elisabet; Jönsen, Andreas; Bengtsson, Christine; Gunnarsson, Iva; Illescas Rodriguez, Vera; Bengtsson, Anders; Arve, Sabine; Rantapää-Dahlqvist, Solbritt; Eloranta, Maija-Leena; Syvänen, Ann-Christine; Sjöwall, Christopher; Vyse, Timothy James; Rönnblom, Lars; Leonard, Dag
• Is Part Of: Annals of the rheumatic diseases. Volume 79:Issue 3(2020)
• Page Start: 363
• Page End: 369
• Publication Date: 2019-12-11
• Subjects: antiphospholipid syndrome -- cardiovascular disease -- gene polymorphism -- lupus nephritis -- systemic lupus erythematosus; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-216227
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE). Methods: 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. Results: 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 –86 and OR 7.48 (6.73 to 8.32), p=2.2×10 –304 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 –5 ), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10 –2 ), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10 –5 ), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10 –3 ), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10 –2 ), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10 –3 ), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10 –2 ), anti-β2 -glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10 –3 ) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10 –2 ) 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 –2 ), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10 –2 ), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10 –7 ), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10 –3 ) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10 –2 ) in high to low quartile comparison. Conclusions: 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.