High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus

Sarah Reid, Andrei Alexsson, Martina Frodlund, David Morris, Johanna K Sandling, Karin Bolin, Elisabet Svenungsson, Andreas Jönsen, Christine Bengtsson, Iva Gunnarsson, Vera Illescas Rodriguez, Anders Bengtsson, Sabine Arve, Solbritt Rantapää-Dahlqvist, Maija-Leena Eloranta, Ann-Christine Syvänen, Christopher Sjöwall, Timothy James Vyse, Lars Rönnblom, Dag Leonard

Research output: Contribution to journalArticlepeer-review

45 Citations (SciVal)

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.

Original languageEnglish
Pages (from-to)363-369
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume79
Issue number3
Early online date2019 Dec 11
DOIs
Publication statusPublished - 2020 Mar

Subject classification (UKÄ)

  • Rheumatology and Autoimmunity

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