Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women
- 5 June 2013
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 73 (6), 1240-1245
- https://doi.org/10.1136/annrheumdis-2012-202675
Abstract
Objectives To identify novel genetic candidates for systemic lupus erythematosus (SLE) in the Korean population, and to validate the risk loci for SLE identified in previous genome-wide association studies (GWAS). Methods We performed a GWAS in 400 Korean female SLE patients and 445 controls. Selected single-nucleotide polymorphisms (SNP) were then replicated in an independent cohort of 385 SLE patients and 583 controls (replication cohort 1), and in a further 811 SLE patients and 1502 controls (replication cohort 2). Results In the GWAS phase, rs9275428 located near HLA-DQB1 showed the strongest association with SLE (OR 0.50, false discovery rate (FDR) p=3.07×10−6). Although no loci reached genome-wide significance outside major histocompatibility complex (MHC), C8orf13-BLK, STAT4, CSMD1, DIAPH3, GLDC and TNFSF4 showed FDR p < 0.05. Our results suggest that STAT4, BLK, IRF5, PTTG1-miR-146a, UBE2L3 and TNFAIP3 are shared susceptibility loci among Caucasians and Asians, while ETS1, IKZF1, SLC15A4 are likely to be Asian-specific loci. In a combined analysis of 1596 SLE patients and 2540 controls for selected 22 candidate SNP, STAT4 and BLK as positive controls showed a strong association with SLE (FDR p=9.85×10−13 and 2.28×10−8, respectively). Of these, 16 candidates (PEX5L, TRAJ50, MYO18B, SOS1, ARHGAP26, SMURF1, CADPS, HAND1, FAM78B, DIAPH3, TBL1XR1, CSMD1, ZBTB20, C3orf21, HIPK1 and AP001042.1) showed only nominal significance (7.05×10−4≤FDR p≤4.38×10−2). Conclusions There are similarities and differences in genetic susceptibility for SLE between Caucasian and Asian ethnic groups. Although 16 putative novel loci for SLE have been suggested in the Korean population, further research on a larger sample is required to discriminate truth from error.This publication has 17 references indexed in Scilit:
- Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the geneGenes & Immunity, 2012
- Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus ErythematosusPLoS Genetics, 2011
- Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosusAnnals Of The Rheumatic Diseases, 2011
- Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus ErythematosusPLoS Genetics, 2010
- Genetic studies of systemic lupus erythematosus in Asia: where are we now?Genes & Immunity, 2009
- Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong ChineseGenes & Immunity, 2009
- Evaluation of imputation-based association in and around the integrin- -M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)Human Molecular Genetics, 2009
- Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosusNature Genetics, 2008
- Ets-1 is a negative regulator of Th17 differentiationThe Journal of Experimental Medicine, 2007
- Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studiesNature Genetics, 2006