title: Evaluation of the relationship and genetic overlap between Kashin-Beck disease and body mass index.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Our results suggest that ADAMTS1 is a novel susceptibility gene for KBD.
authors.affiliation: a 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.
authors.forename: Y
authors.initials: Y
authors.lastname: Wen
authors.affiliation: a 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.
authors.forename: J
authors.initials: J
authors.lastname: Hao
authors.affiliation: a 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.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: a 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.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: a 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.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: b 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.
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.affiliation: c Department of Biostatistics and Bioinformatics , Tulane University School of Public Health and Tropical Medicine , New Orleans , LA , USA.|d Center for Bioinformatics and Genomics , Tulane University , New Orleans , LA , USA.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: c Department of Biostatistics and Bioinformatics , Tulane University School of Public Health and Tropical Medicine , New Orleans , LA , USA.|d Center for Bioinformatics and Genomics , Tulane University , New Orleans , LA , USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.affiliation: e Laboratory of Molecular and Statistical Genetics, College of Life Sciences , Hunan Normal University , Changsha , P. R. China.
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.affiliation: c Department of Biostatistics and Bioinformatics , Tulane University School of Public Health and Tropical Medicine , New Orleans , LA , USA.|d Center for Bioinformatics and Genomics , Tulane University , New Orleans , LA , USA.
authors.forename: H-W
authors.initials: HW
authors.lastname: Deng
authors.affiliation: a 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.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000071097:ADAMTS1 Protein / Q000235:genetics*; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry; D057767:Kashin-Beck Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human