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

作者：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^*

来源：Scientific Reports, 2016, 6(1): 31792.

DOI：10.1038/srep31792

• KNEE OSTEOARTHRITIS
• LINKAGE ANALYSES
• CANDIDATE GENES
• POPULATION
• EXPRESSION
• GROWTH
• TRAIT
• LOCI

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 x 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.

• 出版日期2016-8-22
• 单位西安交通大学; 湖南师范大学; 上海生物信息技术研究中心