Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohortopen access
- Authors
- Bin Joo, Young; Lim, Jiwoo; Tsao, Betty P.; Nath, Swapan K.; Kim, Kwangwoo; Bae, Sang-Cheol
- Issue Date
- Jul-2018
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.8
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 8
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/2345
- DOI
- 10.1038/s41598-018-28128-z
- ISSN
- 2045-2322
- Abstract
- Impact of genetic variants on the age of systemic lupus erythematosus (SLE) onset was not fully understood. We investigated a cumulative effect of SLE-risk variants on the age of SLE onset and scanned genome-wide SNPs to search for new risk loci of childhood-onset SLE (cSLE). We analyzed 781 Korean single-center SLE subjects who previously genotyped by both Immunochip and genome-wide SNP arrays. Individual genetic risk scores (GRS) from well-validated SLE susceptibility loci were calculated and tested for their association with cSLE (<16 years at onset). Single-variant association tests were performed using a multivariable logistic regression adjusting for population stratification. GRS from SLE susceptibility loci was significantly higher in cSLE than aSLE (p = 1.23 x 10⁻³). Two SNPs, rs7460469 in XKR6 (p = 1.26 x 10⁻⁸, OR = 5.58) and rs7300146 in GLT1D1 p = 1.49 x 10⁻⁸, OR = 2.85), showed the most significant associations with cSLE. The model consisting of GRS of SLE and two newly identified loci showed an area under curve (AUC) of 0.71 in a receiver operating characteristics (ROC) curve for prediction of cSLE. In conclusion, cSLE is associated with a high cumulative SLE-risk effect and two novel SNPs rs7460469 and rs7300146, providing the first predictive model for cSLE in Koreans.
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