Causal association between cathepsins and bone mineral density:two-way Mendelian randomization analyses
- VernacularTitle:组织蛋白酶与骨密度的因果关系:双向孟德尔随机化分析
- Author:
Nan JIANG
1
;
Haonan FU
;
Yuhan HAO
;
Zhilin CHEN
;
Zhiqing ZHU
;
Feng XU
;
Dong YU
Author Information
- Publication Type:Journal Article
- Keywords: bone mineral density; cathepsin; Mendelian randomization; causal association; different age groups
- From: Chinese Journal of Tissue Engineering Research 2025;29(12):2623-2630
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Previous studies have indicated that cathepsin K can intervene with the occurrence and development of osteoporosis by regulating bone mineral density in middle-aged and older adults. However,whether there is a causal relationship between the cathepsin family and bone mineral density in other populations remains unknown. OBJECTIVE:To investigate the causal relationship between cathepsin and bone mineral density.METHODS:Genetic loci associated with eight cathepins were extracted from the IEU Open GWAS database as instrumental variables,and bone mineral density values in five age groups acted as an outcome. The causal relationship between cathepin and bone mineral density was assessed by two-way Mendelian randomization analysis. Heterogeneity of the genetic instrumental variables was assessed using Cochran's Q test,pleiotropy was assessed using the MR-Egger intercept test,and the sensitivity of single nucleotide polymorphisms used as instrumental variables to the causal effect of exposure and outcome was assessed using the leave-one-out method. RESULTS AND CONCLUSION:The results of the inverse variance weighting method with positive Mendelian randomization showed that cathepin H was negatively associated with bone mineral density in people aged 45-60 years[odds ratio (95％ confidence interval)=0.965(0.94-0.99),P=0.04];cathepin Z was negatively associated with bone mineral density in people aged 30-45 year[odds ratio (95％ confidence interval)=1.06 (1.00-1.11),P=0.03]. The results of sensitivity analysis showed a stable causal relationship,and MR-Egger intercept analysis did not detect potential horizontal pleiotropy. The inverse Mendelian randomization results showed that bone mineral density had no significant inverse effect on cathepin. The above results confirm that cathepin can affect bone mineral density in some age groups,which may increase the risk of osteoporosis and should be given more attention.
