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Evaluation of the relationship and genetic overlap between Kashin-Beck disease and body mass index.
Scand J Rheumatol. 2016 Nov; 45(6):512-517.SJ

Abstract

OBJECTIVES

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.

METHOD

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+Show Affiliations

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.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.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.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.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.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.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.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.e Laboratory of Molecular and Statistical Genetics, College of Life Sciences , Hunan Normal University , Changsha , P. R. China.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27053287

Citation

Wen, Y, et al. "Evaluation of the Relationship and Genetic Overlap Between Kashin-Beck Disease and Body Mass Index." Scandinavian Journal of Rheumatology, vol. 45, no. 6, 2016, pp. 512-517.
Wen Y, Hao J, Xiao X, et al. Evaluation of the relationship and genetic overlap between Kashin-Beck disease and body mass index. Scand J Rheumatol. 2016;45(6):512-517.
Wen, Y., Hao, J., Xiao, X., Guo, X., Wang, W., Yang, T., Shen, H., Tian, Q., Tan, L., Deng, H. W., & Zhang, F. (2016). Evaluation of the relationship and genetic overlap between Kashin-Beck disease and body mass index. Scandinavian Journal of Rheumatology, 45(6), 512-517.
Wen Y, et al. Evaluation of the Relationship and Genetic Overlap Between Kashin-Beck Disease and Body Mass Index. Scand J Rheumatol. 2016;45(6):512-517. PubMed PMID: 27053287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of the relationship and genetic overlap between Kashin-Beck disease and body mass index. AU - Wen,Y, AU - Hao,J, AU - Xiao,X, AU - Guo,X, AU - Wang,W, AU - Yang,T, AU - Shen,H, AU - Tian,Q, AU - Tan,L, AU - Deng,H-W, AU - Zhang,F, Y1 - 2016/04/07/ PY - 2016/11/2/pubmed PY - 2017/3/16/medline PY - 2016/4/8/entrez SP - 512 EP - 517 JF - Scandinavian journal of rheumatology JO - Scand. J. Rheumatol. VL - 45 IS - 6 N2 - OBJECTIVES: 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. METHOD: 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. SN - 1502-7732 UR - https://www.unboundmedicine.com/medline/citation/27053287/Evaluation_of_the_relationship_and_genetic_overlap_between_Kashin_Beck_disease_and_body_mass_index_ L2 - http://www.tandfonline.com/doi/full/10.3109/03009742.2016.1139742 DB - PRIME DP - Unbound Medicine ER -