Evaluation of the relationship and genetic overlap between Kashin-Beck disease and body mass index

Body mass index (BMI) is one of the major factors affecting the development of osteoarthritis (OA) but there is currently no information available regarding the relationship between BMI and Kashin-Beck disease (KBD). Our aim in this study was to investigate the relationship and genetic overlap between BMI and KBD.

A total of 2050 Han Chinese subjects participated in this study. Using a cohort of 333 grade I KBD patients, logistic regression analysis was conducted to evaluate the correlation between BMI and KBD. Another independent sample of 1717 subjects was genotyped for a genome-wide association study (GWAS) using Affymetrix Human SNP 6.0 Arrays. Single nucleotide polymorphism (SNP) effect concordance analysis (SECA) was applied to the GWAS summaries of KBD and BMI for pleiotropy analysis. Genome-wide bivariate association analysis (GWBAA) of KBD and BMI was carried out to identify the genes with pleiotropic effects on KBD and BMI. The relevance of identified genes with KBD was validated by gene expression profiling and immunohistochemistry.

BMI correlated positively with knee movement disorder in KBD (coefficient β = 0.068, p = 0.045). SECA identified a significant pleiotropic effect (empirical p = 0.021) between KBD and BMI. In the GWBAA, the rs1893577 of the ADAMTS1 gene achieved the most significant association signal (p = 7.38 × 10^-9). ADAMTS1 was also up-regulated in KBD vs. normal (ratio = 2.64 ± 2.80) and KBD vs. OA (ratio = 2.31 ± 2.01). The rate of ADAMTS1-positive chondrocytes in KBD was significantly higher than that in OA (p < 0.05) and healthy controls (p < 0.05).

Our results suggest that ADAMTS1 is a novel susceptibility gene for KBD.