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High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
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2019 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, article id annrheumdis-2019-216227Article in journal (Refereed) Epub ahead of print
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. article id annrheumdis-2019-216227
Keywords [en]
antiphospholipid syndrome, cardiovascular disease, gene polymorphism, lupus nephritis, systemic lupus erythematosus
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-400460DOI: 10.1136/annrheumdis-2019-216227PubMedID: 31826855OAI: oai:DiVA.org:uu-400460DiVA, id: diva2:1381285
Available from: 2019-12-20 Created: 2019-12-20 Last updated: 2019-12-20

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