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Genome-wide assessment of genetic risk for systemic lupus erythematosus and disease severity.

Accepted version
Peer-reviewed

Type

Article

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Authors

Wang, Yong-Fei 
Liu, Lu 
Bielowka, Adrianna 
Ahmed, Rahell 

Abstract

Using three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRSs) for predicting the susceptibility and severity of systemic lupus erythematosus (SLE), using renal disease as a proxy for severity. We used four GWASs to test the performance of GRS both cross validating within the European population and between European and Chinese populations. The performance of GRS in SLE risk prediction was evaluated by receiver operating characteristic (ROC) curves. We then analyzed the polygenic nature of SLE statistically. We also partitioned patients according to their age-of-onset and evaluated the predictability of GRS in disease severity in each age group. We found consistently that the best GRS in the prediction of SLE used SNPs associated at the level of P < 1e-05 in all GWAS data sets and that SNPs with P-values above 0.2 were inflated for SLE true positive signals. The GRS results in an area under the ROC curve ranging between 0.64 and 0.72, within European and between the European and Chinese populations. We further showed a significant positive correlation between a GRS and renal disease in two independent European GWAS (Pcohort1 = 2.44e-08; Pcohort2 = 0.00205) and a significant negative correlation with age of SLE onset (Pcohort1 = 1.76e-12; Pcohort2 = 0.00384). We found that the GRS performed better in the prediction of renal disease in the 'later onset' compared with the 'earlier onset' group. The GRS predicts SLE in both European and Chinese populations and correlates with poorer prognostic factors: young age-of-onset and lupus nephritis.

Description

Keywords

Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lupus Erythematosus, Systemic, Male, Middle Aged, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, Severity of Illness Index, White People

Journal Title

Hum Mol Genet

Conference Name

Journal ISSN

0964-6906
1460-2083

Volume Title

29

Publisher

Oxford University Press (OUP)

Rights

All rights reserved
Sponsorship
Medical Research Council (MR/M01665X/1)
China Scholarship Council (CSC) & National Science Foundation of China grant 81801636