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

Hye Soon Lee, Taehyeung Kim, So Young Bang, Young Ji Na, Il Kim, Kwangwoo Kim, Jae Hoon Kim, Yeun Jun Chung, Hyoung Doo Shin, Young Mo Kang, Seung Cheol Shim, Chang Hee Suh, Yong Beom Park, Jong Sung Kim, Changwon Kang, Sang Cheol Bae

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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 singlenucleotide 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.

Original languageEnglish
Pages (from-to)1240-1245
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume73
Issue number6
DOIs
Publication statusPublished - 2014 Jun

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Genome-Wide Association Study
Systemic Lupus Erythematosus
Genes
Polymorphism
Genetic Predisposition to Disease
Major Histocompatibility Complex
Ethnic Groups
Population
Genome

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lee, Hye Soon ; Kim, Taehyeung ; Bang, So Young ; Na, Young Ji ; Kim, Il ; Kim, Kwangwoo ; Kim, Jae Hoon ; Chung, Yeun Jun ; Shin, Hyoung Doo ; Kang, Young Mo ; Shim, Seung Cheol ; Suh, Chang Hee ; Park, Yong Beom ; Kim, Jong Sung ; Kang, Changwon ; Bae, Sang Cheol. / Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women. In: Annals of the Rheumatic Diseases. 2014 ; Vol. 73, No. 6. pp. 1240-1245.
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title = "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 singlenucleotide 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.",
author = "Lee, {Hye Soon} and Taehyeung Kim and Bang, {So Young} and Na, {Young Ji} and Il Kim and Kwangwoo Kim and Kim, {Jae Hoon} and Chung, {Yeun Jun} and Shin, {Hyoung Doo} and Kang, {Young Mo} and Shim, {Seung Cheol} and Suh, {Chang Hee} and Park, {Yong Beom} and Kim, {Jong Sung} and Changwon Kang and Bae, {Sang Cheol}",
year = "2014",
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doi = "10.1136/annrheumdis-2012-202675",
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Lee, HS, Kim, T, Bang, SY, Na, YJ, Kim, I, Kim, K, Kim, JH, Chung, YJ, Shin, HD, Kang, YM, Shim, SC, Suh, CH, Park, YB, Kim, JS, Kang, C & Bae, SC 2014, 'Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women', Annals of the Rheumatic Diseases, vol. 73, no. 6, pp. 1240-1245. https://doi.org/10.1136/annrheumdis-2012-202675

Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women. / Lee, Hye Soon; Kim, Taehyeung; Bang, So Young; Na, Young Ji; Kim, Il; Kim, Kwangwoo; Kim, Jae Hoon; Chung, Yeun Jun; Shin, Hyoung Doo; Kang, Young Mo; Shim, Seung Cheol; Suh, Chang Hee; Park, Yong Beom; Kim, Jong Sung; Kang, Changwon; Bae, Sang Cheol.

In: Annals of the Rheumatic Diseases, Vol. 73, No. 6, 06.2014, p. 1240-1245.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women

AU - Lee, Hye Soon

AU - Kim, Taehyeung

AU - Bang, So Young

AU - Na, Young Ji

AU - Kim, Il

AU - Kim, Kwangwoo

AU - Kim, Jae Hoon

AU - Chung, Yeun Jun

AU - Shin, Hyoung Doo

AU - Kang, Young Mo

AU - Shim, Seung Cheol

AU - Suh, Chang Hee

AU - Park, Yong Beom

AU - Kim, Jong Sung

AU - Kang, Changwon

AU - Bae, Sang Cheol

PY - 2014/6

Y1 - 2014/6

N2 - 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 singlenucleotide 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.

AB - 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 singlenucleotide 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.

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