Chinese Journal of Endocrinology and Metabolism · Oct 25, 2026
Causal relationship between the lipidome and osteoporosis mediated by immune cells: A Mendelian randomization study
By 赵丹, 姚波, 李凌新 et al.
Objective To explore the potential causal relationship between the lipidome and osteoporosis(OP) based on Mendelian randomization(MR), and to reveal the mediating role of immune cells.Methods Single nucleotide polymorphism data related to lipids, immune cells, and OP were obtained from public genome-wide association study(GWAS) databases. The inverse variance weighted(IVW) method was mainly adopted for analysis, and Cochran′s test was used to identify whether there was heterogeneity in the MR results. The horizontal pleiotropy was evaluated simultaneously by the MR-PRESSO global test method and the MR-Egger intercept method. Results Using the IVW method as the main analytical approach and after correction by the false discovery rate(FDR), it was finally identified that there were causal relationships between 7 lipids and OP. Among them, 5 lipids were risk factors for OP, and 2 were protective factors. We found that diacylglycerol(18: 1_18: 1; =1.17, 95% 1.08-1.27, FDR-corrected =0.001) was the most significant risk-associated lipid for OP. In addition, a total of seven immune cells with causal associations with OP were identified, including three risk factors and four protective factors. Among them, CD127 CD45RA CD4 regulatory T cells( =0.92, 95% 0.88-0.96, FDR-corrected =0.003) were the most significant protective factor for OP. Although mediation analysis showed that the effect of diacylglycerol(18: 1_18: 1) on OP through CD127 CD45RA CD4 regulatory T cells was not statistically significant( >0.05), the impact of lipids on OP through immune cells still has certain research value. Conclusion This study reveals potential causal relationships between multiple lipids and immune cells with OP, providing a new perspective on lipid-immune cell-bone research. These findings are expected to identify potential biomarkers for OP and provide new directions for its prevention, diagnosis and treatment.