A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease

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...

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Main Authors:	Hao, Jingcan, Wang, Wenyu, Wen, Yan, Xiao, Xiao, He, Awen, Guo, Xiong, Yang, Tielin, Liu, Xiaogang, Shen, Hui, Chen, Xiangding, Tian, Qing, Deng, Hong-Wen, Zhang, Feng
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992896/

id	pubmed-4992896
recordtype	oai_dc
spelling	pubmed-49928962016-08-30 A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease Hao, Jingcan Wang, Wenyu Wen, Yan Xiao, Xiao He, Awen Guo, Xiong Yang, Tielin Liu, Xiaogang Shen, Hui Chen, Xiangding Tian, Qing Deng, Hong-Wen Zhang, Feng Article 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. Nature Publishing Group 2016-08-22 /pmc/articles/PMC4992896/ /pubmed/27545300 http://dx.doi.org/10.1038/srep31792 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hao, Jingcan Wang, Wenyu Wen, Yan Xiao, Xiao He, Awen Guo, Xiong Yang, Tielin Liu, Xiaogang Shen, Hui Chen, Xiangding Tian, Qing Deng, Hong-Wen Zhang, Feng
spellingShingle	Hao, Jingcan Wang, Wenyu Wen, Yan Xiao, Xiao He, Awen Guo, Xiong Yang, Tielin Liu, Xiaogang Shen, Hui Chen, Xiangding Tian, Qing Deng, Hong-Wen Zhang, Feng A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
author_facet	Hao, Jingcan Wang, Wenyu Wen, Yan Xiao, Xiao He, Awen Guo, Xiong Yang, Tielin Liu, Xiaogang Shen, Hui Chen, Xiangding Tian, Qing Deng, Hong-Wen Zhang, Feng
author_sort	Hao, Jingcan
title	A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
title_short	A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
title_full	A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
title_fullStr	A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
title_full_unstemmed	A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
title_sort	bivariate genome-wide association study identifies adam12 as a novel susceptibility gene for kashin-beck disease
description	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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992896/
_version_	1613631695988195328

A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease

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