In:
Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. 3 ( 2020-03), p. 363-369
Abstract:
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-β 2 -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.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2019-216227
Language:
English
Publisher:
BMJ
Publication Date:
2020
detail.hit.zdb_id:
1481557-6
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