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Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin–Beck disease

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Abstract

Kashin–Beck disease (KBD) is a chronic osteochondropathy. In this study, we conducted the first genome-wide copy number variation study (GCNVS) of KBD totally involving 2,743 Chinese Han adults. GCNVS was first performed using Affymetrix Human SNP6.0 Arrays. The identified copy number variations (CNVs) were then replicated in an independent Chinese Han sample containing 1,026 subjects. SNP genotyping, CNV identification and quality control were implemented by Birdsuite. STRUCTURE and EIGENSTRAT were applied for controlling potential population stratification in the GCNVS. Association analysis was conducted using PLINK. Microarray and qRT-PCR were also conducted to compare the expression levels of the genes overlapping with identified CNVs between KBD patients and healthy controls. GCNVS found that CNV452 (P value = 7.78 × 10−5) overlapping with ABI3BP gene was significantly associated with KBD. Replication association study observed that rs9850273 (P value = 0.008) and rs7613610 (P value = 0.021) in ABI3BP gene were significantly associated with KBD. Gene expression analysis also found that ABI3BP was up-regulated in KBD patients compared to healthy controls. Our results suggest that ABI3BP was a novel susceptibility gene for KBD.

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Acknowledgments

The study was supported by National Natural Scientific Fund of China (81102086), Science and Technology Research and Development Program of Shaanxi Province (2013KJXX-51), Natural Science Basic Research Program of Shaanxi Province (2011JQ4013) and the Fundamental Research Funds for the Central Universities.

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Authors and Affiliations

  1. Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Faculty of Public Health, College of Medicine, Xi’an Jiaotong University, Xi’an, People’s Republic of China

    Feng Zhang, Xiong Guo, Yinping Zhang, Yan Wen & Sen Wang

  2. Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, People’s Republic of China

    Weizhuo Wang

  3. Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China

    Tielin Yang

  4. Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA

    Hui Shen, Qing Tian & Hong-Wen Deng

  5. Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA

    Hui Shen, Qing Tian & Hong-Wen Deng

  6. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China

    Xiangding Chen & Lijun Tan

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  1. Feng Zhang
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  2. Xiong Guo
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  8. Hui Shen
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  9. Xiangding Chen
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  10. Qing Tian
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  11. Lijun Tan
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  12. Hong-Wen Deng
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Corresponding author

Correspondence to Xiong Guo.

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Supporting Information:

Table S1. List of identified CNVs with association testing P value <0.05

Fig. S1. STRUCTURE triangle plot (K = 3) of population stratification analysis.

Supplementary material 1 (DOC 48 kb)

Supplementary material 2 (TIFF 423 kb)

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Zhang, F., Guo, X., Zhang, Y. et al. Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin–Beck disease. Hum Genet 133, 793–799 (2014). https://doi.org/10.1007/s00439-014-1418-4

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  • DOI: https://doi.org/10.1007/s00439-014-1418-4

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