Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease

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Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease. / Lee, Yun Jong; Horie, Yukihiro; Wallace, Graham R; Choi, Yong Seok; Park, Ji Ah; Choi, Ji Yong; Song, Ran; Kang, Young-Mo; Kang, Seong Wook; Baek, Han Joo; Kitaichi, Nobuyoshi; Meguro, Akira; Mizuki, Nobuhisa; Namba, Kenichi; Ishida, Susumu; Kim, Jinhyun; Niemczyk, Edyta; Lee, Eun Young; Song, Yeong Wook; Ohno, Shigeaki; Lee, Eun Bong.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 9, 01.09.2013, p. 1510-6.

Research output: Contribution to journalArticle

Harvard

Lee, YJ, Horie, Y, Wallace, GR, Choi, YS, Park, JA, Choi, JY, Song, R, Kang, Y-M, Kang, SW, Baek, HJ, Kitaichi, N, Meguro, A, Mizuki, N, Namba, K, Ishida, S, Kim, J, Niemczyk, E, Lee, EY, Song, YW, Ohno, S & Lee, EB 2013, 'Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease', Annals of the Rheumatic Diseases, vol. 72, no. 9, pp. 1510-6. https://doi.org/10.1136/annrheumdis-2011-200288

APA

Lee, Y. J., Horie, Y., Wallace, G. R., Choi, Y. S., Park, J. A., Choi, J. Y., Song, R., Kang, Y-M., Kang, S. W., Baek, H. J., Kitaichi, N., Meguro, A., Mizuki, N., Namba, K., Ishida, S., Kim, J., Niemczyk, E., Lee, E. Y., Song, Y. W., ... Lee, E. B. (2013). Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease. Annals of the Rheumatic Diseases, 72(9), 1510-6. https://doi.org/10.1136/annrheumdis-2011-200288

Vancouver

Author

Lee, Yun Jong ; Horie, Yukihiro ; Wallace, Graham R ; Choi, Yong Seok ; Park, Ji Ah ; Choi, Ji Yong ; Song, Ran ; Kang, Young-Mo ; Kang, Seong Wook ; Baek, Han Joo ; Kitaichi, Nobuyoshi ; Meguro, Akira ; Mizuki, Nobuhisa ; Namba, Kenichi ; Ishida, Susumu ; Kim, Jinhyun ; Niemczyk, Edyta ; Lee, Eun Young ; Song, Yeong Wook ; Ohno, Shigeaki ; Lee, Eun Bong. / Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease. In: Annals of the Rheumatic Diseases. 2013 ; Vol. 72, No. 9. pp. 1510-6.

Bibtex

@article{5e08ef34647741aaae292f7d12ec69f6,
title = "Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease",
abstract = "OBJECTIVES: To identify non-major histocompatibility complex susceptible genes that might contribute to Beh{\c c}et's disease (BD).METHODS: We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated.RESULTS: We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60×10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67×10(-4)) and rs10256482 (OR=1.27, p=5.27×10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53×10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis.CONCLUSIONS: These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.",
keywords = "Adult, Asian Continental Ancestry Group, Behcet Syndrome, Cell Survival, Chromosome Mapping, Chromosomes, Human, Pair 7, Female, GTP-Binding Proteins, Gene Knockdown Techniques, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Japan, Male, Polymorphism, Single Nucleotide, RNA Interference, RNA, Messenger, T-Lymphocytes",
author = "Lee, {Yun Jong} and Yukihiro Horie and Wallace, {Graham R} and Choi, {Yong Seok} and Park, {Ji Ah} and Choi, {Ji Yong} and Ran Song and Young-Mo Kang and Kang, {Seong Wook} and Baek, {Han Joo} and Nobuyoshi Kitaichi and Akira Meguro and Nobuhisa Mizuki and Kenichi Namba and Susumu Ishida and Jinhyun Kim and Edyta Niemczyk and Lee, {Eun Young} and Song, {Yeong Wook} and Shigeaki Ohno and Lee, {Eun Bong}",
year = "2013",
month = sep
day = "1",
doi = "10.1136/annrheumdis-2011-200288",
language = "English",
volume = "72",
pages = "1510--6",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease

AU - Lee, Yun Jong

AU - Horie, Yukihiro

AU - Wallace, Graham R

AU - Choi, Yong Seok

AU - Park, Ji Ah

AU - Choi, Ji Yong

AU - Song, Ran

AU - Kang, Young-Mo

AU - Kang, Seong Wook

AU - Baek, Han Joo

AU - Kitaichi, Nobuyoshi

AU - Meguro, Akira

AU - Mizuki, Nobuhisa

AU - Namba, Kenichi

AU - Ishida, Susumu

AU - Kim, Jinhyun

AU - Niemczyk, Edyta

AU - Lee, Eun Young

AU - Song, Yeong Wook

AU - Ohno, Shigeaki

AU - Lee, Eun Bong

PY - 2013/9/1

Y1 - 2013/9/1

N2 - OBJECTIVES: To identify non-major histocompatibility complex susceptible genes that might contribute to Behçet's disease (BD).METHODS: We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated.RESULTS: We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60×10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67×10(-4)) and rs10256482 (OR=1.27, p=5.27×10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53×10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis.CONCLUSIONS: These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.

AB - OBJECTIVES: To identify non-major histocompatibility complex susceptible genes that might contribute to Behçet's disease (BD).METHODS: We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated.RESULTS: We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60×10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67×10(-4)) and rs10256482 (OR=1.27, p=5.27×10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53×10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis.CONCLUSIONS: These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.

KW - Adult

KW - Asian Continental Ancestry Group

KW - Behcet Syndrome

KW - Cell Survival

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 7

KW - Female

KW - GTP-Binding Proteins

KW - Gene Knockdown Techniques

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Japan

KW - Male

KW - Polymorphism, Single Nucleotide

KW - RNA Interference

KW - RNA, Messenger

KW - T-Lymphocytes

U2 - 10.1136/annrheumdis-2011-200288

DO - 10.1136/annrheumdis-2011-200288

M3 - Article

C2 - 23041938

VL - 72

SP - 1510

EP - 1516

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 9

ER -