两样本孟德尔随机化研究炎症因子与骨质疏松症的 因果关联.

Objective To assess the causal relationship between inflammatory factors and osteoporosis (OP), Methods GWAS data for 41 inflammatory factors and bone mineral density (BMD) were obtained from the GWAS catalog database and OP GWAS data were obtained from the Finnish database. Mendelian randomization analysis was conducted using inverse variance weighted method. (IVW), MR-Egger regression (MER), weighted median method (WME), simple median method and weighted mode method. IVW was primarily employed for analysis. Sensitivity analysis was performed to assess the reliability of result. The impact of single nucleotide polymorphisms on the outcome was evaluated using sleave-one-out analysis. Finally, drug prediction and molecular docking were conducted to further validate the pharmacological value of inflammatory factors. Results The study indicated a causal relationship between inflammatory factors and OP and BMD. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and monocyte chemoattractant protein-1 (MCP-1/MCAF) were positively associated with the risk of developing OP. Tumor necrosis factor β (TNF-B) was negatively associated with BMD in individuals aged 0-15. Interleukin-7 (IL-7) was negatively associated with BMD in individuals aged 15-30. Hepatocyte growth factor (HGF) was negatively associated with BMD in individuals aged 30-45. Macrophage inflammatory protein la (MIP-1a) and macrophage colony-stimulating factor (M-CSF) were negatively associated with BMD in individuals aged over 60. MIP-la was negatively associated with BMD across all age groups. Additionally, molecular docking confirmed the favorable binding between the drugs and proteins, further validating the pharmacological value of these targets. Conclusion The MR approach comprehensively evaluates the causal effects of 41 inflammatory factors on OP and BMD, indicating a causal association between inflammatory factors and OP and BMD. This suggests that intervention in inflammatory factors in the early stages of the disease could influence the development and progression of OP. [ABSTRACT FROM AUTHOR]