Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with diverse heterogeneous phenotypes. Although many studies of SLE presented estimates of high heritability, impact of complex genetic variants on the clinical manifestations and antibodies profiles of SLE was not fully understood. The aim of this study is to identify the genetic load by genetic risk score (GRS) that influence the clinical and serological manifestations according to ACR criteria in patients with SLE.
Methods: A total of 781 Korean patients from the Hanyang BAE lupus cohort were genotyped by genome-wide association study array. Weighted genetic risk score (GRS) were calculated from 45 well-validated non-HLA SNPs and HLA SLE-risk loci. Individual GRS was tested for associations with the clinical subphenotypes based on ACR criteria of SLE and the development of autoantibody by using a multivariable linear regression or a logistic regression.
Results: We identified weighted GRS calculated from non-HLA and HLA SLE-risk loci with significant associations in various SLE subphenotypes defined by the ACR criteria (mean number 5.74) among 11 criteria. Individual’s weighted GRS showed significantly positive correlation with the number of ACR criteria in a linear regression model (β coefficient = 0.13, p = 9.00×10−3). Consistently, a significant positive correlation with the number of ACR in both non-HLA GRS (β = 0.11, p = 0.027) and HLA GRS (β 0.06, p = 0.021) was observed, respectively.
In a clinical subphenotype analysis, weighted GRS from non-HLA and HLA risk loci were significantly related to malar rash (OR 1.23, p = 2.68×10−3), renal disorder (OR 1.15, p = 4.41×10−2), and thrombocytopenia (OR 1.21, p = 7.55×10−3) using a multivariable logistic regression. Weighted GRS were strongly associated with production of anti-DNA antibody (OR 1.38, p = 2.18×10−3).
In conclusion, genetic risk load of SLE is significantly higher in individuals with more diverse clinical and serological manifestations. Several subphenotypes (malar rash, renal disorder, thrombocytopenia and anti-dsDNA antibody) might be influenced by cumulative genetic risk load.
To cite this abstract in AMA style:Bang S, Ha E, Kwon H, Yoo H, Kang J, Kim J, Nam B, Shin J, Lee Y, Lee T, Lee H, Kim K, Bae S. Higher Genetic Risk Load in Patients with More Diverse Manifestations in a Korean Systemic Lupus Erythematosus Cohort [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/higher-genetic-risk-load-in-patients-with-more-diverse-manifestations-in-a-korean-systemic-lupus-erythematosus-cohort/. Accessed December 5, 2020.
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