title: Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, , Seoul, Korea.
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Lee
authors.forename: Taehyeung
authors.initials: T
authors.lastname: Kim
authors.forename: So Young
authors.initials: SY
authors.lastname: Bang
authors.forename: Young Ji
authors.initials: YJ
authors.lastname: Na
authors.forename: Il
authors.initials: I
authors.lastname: Kim
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Kim
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
authors.forename: Yong-Beom
authors.initials: YB
authors.lastname: Park
authors.forename: Jong-Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Changwon
authors.initials: C
authors.lastname: Kang
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea / Q000208:ethnology; D012737:Sex Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
keywords: Autoimmunity; Epidemiology; Systemic Lupus Erythematosus