RT Journal Article SR Electronic T1 High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus JF Annals of the Rheumatic Diseases JO Ann Rheum Dis FD BMJ Publishing Group Ltd and European League Against Rheumatism SP 363 OP 369 DO 10.1136/annrheumdis-2019-216227 VO 79 IS 3 A1 Sarah Reid A1 Andrei Alexsson A1 Martina Frodlund A1 David Morris A1 Johanna K Sandling A1 Karin Bolin A1 Elisabet Svenungsson A1 Andreas Jönsen A1 Christine Bengtsson A1 Iva Gunnarsson A1 Vera Illescas Rodriguez A1 Anders Bengtsson A1 Sabine Arve A1 Solbritt Rantapää-Dahlqvist A1 Maija-Leena Eloranta A1 Ann-Christine Syvänen A1 Christopher Sjöwall A1 Timothy James Vyse A1 Lars Rönnblom A1 Dag Leonard YR 2020 UL http://ard.bmj.com/content/79/3/363.abstract AB 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.