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A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease.
Sci Rep. 2016 08 22; 6:31792.SR

Abstract

Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 × 10(-9)) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 ± 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 ± 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD.

Authors+Show Affiliations

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.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, P.R. China.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, P.R. China.Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA. Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana, USA.Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, P. R. China.Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA. Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana, USA.Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA. Center for Bioinformatics and Genomics, Tulane University, New Orleans, Louisiana, USA.Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science center, Xi'an Jiaotong University, Xi'an, P. R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27545300

Citation

Hao, Jingcan, et al. "A Bivariate Genome-wide Association Study Identifies ADAM12 as a Novel Susceptibility Gene for Kashin-Beck Disease." Scientific Reports, vol. 6, 2016, p. 31792.
Hao J, Wang W, Wen Y, et al. A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease. Sci Rep. 2016;6:31792.
Hao, J., Wang, W., Wen, Y., Xiao, X., He, A., Guo, X., Yang, T., Liu, X., Shen, H., Chen, X., Tian, Q., Deng, H. W., & Zhang, F. (2016). A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease. Scientific Reports, 6, 31792. https://doi.org/10.1038/srep31792
Hao J, et al. A Bivariate Genome-wide Association Study Identifies ADAM12 as a Novel Susceptibility Gene for Kashin-Beck Disease. Sci Rep. 2016 08 22;6:31792. PubMed PMID: 27545300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease. AU - Hao,Jingcan, AU - Wang,Wenyu, AU - Wen,Yan, AU - Xiao,Xiao, AU - He,Awen, AU - Guo,Xiong, AU - Yang,Tielin, AU - Liu,Xiaogang, AU - Shen,Hui, AU - Chen,Xiangding, AU - Tian,Qing, AU - Deng,Hong-Wen, AU - Zhang,Feng, Y1 - 2016/08/22/ PY - 2016/02/29/received PY - 2016/07/26/accepted PY - 2016/8/23/entrez PY - 2016/8/23/pubmed PY - 2018/5/16/medline SP - 31792 EP - 31792 JF - Scientific reports JO - Sci Rep VL - 6 N2 - Kashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 × 10(-9)) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 ± 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 ± 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/27545300/A_bivariate_genome_wide_association_study_identifies_ADAM12_as_a_novel_susceptibility_gene_for_Kashin_Beck_disease_ L2 - http://dx.doi.org/10.1038/srep31792 DB - PRIME DP - Unbound Medicine ER -