Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort.
Sci Rep. 2018 Jul 02; 8(1):9962.SR

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.

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Authors+Show Affiliations

Joo YB

Department of Rheumatology, St. Vincent's Hospital, The Catholic University of Korea, Suwon, Republic of Korea.

Lim J

Department of Biology, Kyung Hee University, Seoul, Republic of Korea.

Tsao BP

Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Nath SK

Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.

Kim K

Department of Biology, Kyung Hee University, Seoul, Republic of Korea. kkim@khu.ac.kr.

Bae SC

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea. scbae@hanyang.ac.kr.

MeSH

AdolescentAge of OnsetAsian PeopleChildCohort StudiesFemaleGalactosyltransferasesGenetic Predisposition to DiseaseHumansLupus Erythematosus, SystemicMaleModels, GeneticPolymorphism, Single NucleotideROC Curve

Pub Type(s)

Journal Article

Research Support, N.I.H., Extramural

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29967481

Citation

Joo, Young Bin, et al. "Genetic Variants in Systemic Lupus Erythematosus Susceptibility Loci, XKR6 and GLT1D1 Are Associated With Childhood-onset SLE in a Korean Cohort." Scientific Reports, vol. 8, no. 1, 2018, p. 9962.

Joo YB, Lim J, Tsao BP, et al. Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort. Sci Rep. 2018;8(1):9962.

Joo, Y. B., Lim, J., Tsao, B. P., Nath, S. K., Kim, K., & Bae, S. C. (2018). Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort. Scientific Reports, 8(1), 9962. https://doi.org/10.1038/s41598-018-28128-z

Joo YB, et al. Genetic Variants in Systemic Lupus Erythematosus Susceptibility Loci, XKR6 and GLT1D1 Are Associated With Childhood-onset SLE in a Korean Cohort. Sci Rep. 2018 07 2;8(1):9962. PubMed PMID: 29967481.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort. AU - Joo,Young Bin, AU - Lim,Jiwoo, AU - Tsao,Betty P, AU - Nath,Swapan K, AU - Kim,Kwangwoo, AU - Bae,Sang-Cheol, Y1 - 2018/07/02/ PY - 2018/03/06/received PY - 2018/06/15/accepted PY - 2018/7/4/entrez PY - 2018/7/4/pubmed PY - 2019/10/24/medline SP - 9962 EP - 9962 JF - Scientific reports JO - Sci Rep VL - 8 IS - 1 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/29967481/full_citation DB - PRIME DP - Unbound Medicine ER -

Tags

Genetic variants in systemic lupus erythematosus susceptibility loci, XKR6 and GLT1D1 are associated with childhood-onset SLE in a Korean cohort.Sci Rep. 2018 Jul 02; 8(1):9962.SR