OBJECTIVE: to investigate the causal relationship between lipid metabolites and heel bone mineral density using two-sample Mendelian randomization analysis.
METHODS: Summary-level data from large-scale genome-wide association studies were extracted to identify genetic variants linked to lipid metabolite levels. These genetic variants were subsequently employed as instrumental variables in Mendelian randomization analysis to estimate the causal effects of each lipid metabolite on heel bone mineral density. Furthermore, metabolites that could potentially be influenced by causal relationships with bone mineral density were extracted from the KEGG and WikiPathways databases. The causal associations between these downstream metabolites and heel bone mineral density were then examined. Lastly, a sensitivity analysis was conducted to evaluate the robustness of the results and address potential sources of bias.
RESULTS: A total of 130 lipid metabolites were analyzed, and it was found that acetylcarnitine, propionylcarnitine, hexadecanedioate, tetradecanedioate, myo-inositol, 1-arachidonoylglycerophosphorine, 1-linoleoylglycerophoethanolamine, and epiandrosterone sulfate had a causal relationship with heel bone mineral density (p < 0.05). Furthermore, our findings also indicate an absence of causal association between the downstream metabolites associated with the aforementioned metabolites identified in the KEGG and WikiPathways databases and heel bone mineral density.
CONCLUSIONS: This work supports the hypothesis that lipid metabolites have an impact on bone health through demonstrating a causal relationship between specific lipid metabolites and heel bone mineral density. This study has significant implications for the development of new strategies to osteoporosis prevention and treatment.
目的:使用双样本孟德尔随机分析来研究脂质代谢产物与足跟骨密度之间的因果关系。
方法:提取来自大规模全基因组关联研究的汇总水平数据,以鉴定与脂质代谢物水平相关的遗传变异。这些遗传变异随后被用作孟德尔随机化分析的工具变量,以估计每种脂质代谢物对脚跟骨矿物质密度的因果影响。此外,从KEGG和WikiPathways数据库中提取了可能受与骨矿物质密度因果关系影响的代谢物.然后检查这些下游代谢物与脚跟骨矿物质密度之间的因果关系。最后,我们进行了敏感性分析,以评估结果的稳健性并解决潜在的偏倚来源.
结果:共分析了130种脂质代谢物,结果发现乙酰肉碱,丙酰肉碱,十六烷二酸酯,十四烷二酸酯,肌醇,1-花生四酰基甘油磷酸,1-亚油酰基甘油乙醇胺,硫酸表雄酮与足跟骨密度有因果关系(p<0.05)。此外,我们的研究结果还表明,在KEGG和WikiPathways数据库中,与上述代谢物相关的下游代谢物与足跟骨矿物质密度之间不存在因果关系.
结论:这项工作通过证明特定脂质代谢物与足跟骨矿物质密度之间的因果关系,支持脂质代谢物对骨骼健康有影响的假设。这项研究对开发骨质疏松症预防和治疗的新策略具有重要意义。