Brief report: Genome-wide association study identifies ITPR2 as a Susceptibility gene for Kashin-beck disease in Han Chinese

Feng Zhang; Yan Wen; Xiong Guo; Yingang Zhang; Xi Wang; Tielin Yang; Hui Shen; Xiangding Chen; Qing Tian; Hong Wen Deng

doi:10.1002/art.38898

Brief report: Genome-wide association study identifies ITPR2 as a Susceptibility gene for Kashin-beck disease in Han Chinese

Feng Zhang
, Yan Wen
, Xiong Guo
, Yingang Zhang
, Xi Wang
, Tielin Yang
, Hui Shen
, Xiangding Chen
, Qing Tian
, Hong Wen Deng

School of Life Science and Technology (SLST)

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Objective Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS) .

Methods Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.

Results The GWAS identified significant association (P = 1.58 × 10^-8) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10^-3), rs16931011 (P = 1.29 × 10^-3), rs1531928 (P = 4.95 × 10^-3), rs4414322 (P = 4.40 × 10^-3), rs11048570 (P = 4.53 × 10^-3), rs11048572 (P = 4.43 × 10^-3), rs2017510 (P = 4.58 × 10^-3), rs9669395 (P = 5.77 × 10^-3), and rs1002835 (P = 4.85 × 10^-3). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013) .

Conclusion Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.

Original language	English
Pages (from-to)	176-181
Number of pages	6
Journal	Arthritis and Rheumatology
Volume	67
Issue number	1
DOIs	https://doi.org/10.1002/art.38898
State	Published - 1 Jan 2015

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@article{447486cf486543cf9e5c00a28c54cc57,

title = "Brief report: Genome-wide association study identifies ITPR2 as a Susceptibility gene for Kashin-beck disease in Han Chinese",

abstract = "Objective Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS) .Methods Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.Results The GWAS identified significant association (P = 1.58 × 10-8) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10-3), rs16931011 (P = 1.29 × 10-3), rs1531928 (P = 4.95 × 10-3), rs4414322 (P = 4.40 × 10-3), rs11048570 (P = 4.53 × 10-3), rs11048572 (P = 4.43 × 10-3), rs2017510 (P = 4.58 × 10-3), rs9669395 (P = 5.77 × 10-3), and rs1002835 (P = 4.85 × 10-3). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013) .Conclusion Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.",

author = "Feng Zhang and Yan Wen and Xiong Guo and Yingang Zhang and Xi Wang and Tielin Yang and Hui Shen and Xiangding Chen and Qing Tian and Deng, \{Hong Wen\}",

note = "Publisher Copyright: {\textcopyright} 2015 The Authors. Arthritis \& Rheumatology is published by Wiley Periodicals, Inc.",

year = "2015",

month = jan,

day = "1",

doi = "10.1002/art.38898",

language = "英语",

volume = "67",

pages = "176--181",

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T1 - Brief report

T2 - Genome-wide association study identifies ITPR2 as a Susceptibility gene for Kashin-beck disease in Han Chinese

AU - Zhang, Feng

AU - Wen, Yan

AU - Guo, Xiong

AU - Zhang, Yingang

AU - Wang, Xi

AU - Yang, Tielin

AU - Shen, Hui

AU - Chen, Xiangding

AU - Tian, Qing

AU - Deng, Hong Wen

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Objective Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS) .Methods Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.Results The GWAS identified significant association (P = 1.58 × 10-8) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10-3), rs16931011 (P = 1.29 × 10-3), rs1531928 (P = 4.95 × 10-3), rs4414322 (P = 4.40 × 10-3), rs11048570 (P = 4.53 × 10-3), rs11048572 (P = 4.43 × 10-3), rs2017510 (P = 4.58 × 10-3), rs9669395 (P = 5.77 × 10-3), and rs1002835 (P = 4.85 × 10-3). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013) .Conclusion Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.

AB - Objective Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS) .Methods Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.Results The GWAS identified significant association (P = 1.58 × 10-8) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10-3), rs16931011 (P = 1.29 × 10-3), rs1531928 (P = 4.95 × 10-3), rs4414322 (P = 4.40 × 10-3), rs11048570 (P = 4.53 × 10-3), rs11048572 (P = 4.43 × 10-3), rs2017510 (P = 4.58 × 10-3), rs9669395 (P = 5.77 × 10-3), and rs1002835 (P = 4.85 × 10-3). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013) .Conclusion Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.

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DO - 10.1002/art.38898

M3 - 文章

C2 - 25303641

AN - SCOPUS:84919883616

SN - 2326-5191

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JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

IS - 1

ER -

Brief report: Genome-wide association study identifies ITPR2 as a Susceptibility gene for Kashin-beck disease in Han Chinese

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