Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort

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 × 10⁻³). Two SNPs, rs7460469 in XKR6 (p = 1.26 × 10⁻⁸, OR = 5.58) and rs7300146 in GLT1D1 p = 1.49 × 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.