Association between bone mineral density in different age groups and primary malignant bone tumor: a Mendelian randomization study
10.19485/j.cnki.issn2096-5087.2025.06.015
- Author:
WANG Manyi
;
WU Jingjing
;
LI Xiaoshan
;
ZHANG Huiru
;
HUANG Zhikai
;
ZENG Guqing
- Publication Type:Journal Article
- Keywords:
bone mineral density;
primary malignant bone tumor;
Mendelian randomization;
enrichment analysis
- From:
Journal of Preventive Medicine
2025;37(6):612-615
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor.
Methods:The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.
Results:The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes.
Conclusion:The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.
- Full text:2025110608575852382不同年龄分组的骨密度与原发性恶性骨肿瘤的孟德尔随机化研究.pdf
