Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women.

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=3.07x10(-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=9.85x10(-13) and

2.28x10(-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 (7.05x10(-4)</=FDR

p</=4.38x10(-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.