孟德尔随机化分析血液代谢物与肌少症相关特征的因果关系  

Causal relationship between blood metabolites and sarcopenia-related traits:a Mendelian randomization study

作　　者：陈天鑫 董婷婷 李妍 张晟[1] 张磊[1] Chen Tianxin;Dong Tingting;Li Yan;Zhang Sheng;Zhang Lei(The Forth Department of Bone and Joint,Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]中国中医科学院望京医院骨关节四科,北京市100102

出　　处：《中国组织工程研究》2024年第27期4288-4292,共5页Chinese Journal of Tissue Engineering Research

摘　　要：背景:临床证据显示代谢因素与肌少症之间存在相关性,血液代谢物已被用于揭示肌肉骨骼疾病的生物学机制,然而血液代谢物与肌少症之间的因果关系尚不明确。目的:运用两样本孟德尔随机化分析方法探讨血液代谢物与肌少症相关特征之间的因果关系,分析其代谢通路。方法:从公共数据库获取486种血液代谢物与肌少症相关特征的数据集。运用逆方差加权、MR-Egger和加权中位数法评估血液代谢物与不同性别肌量、肌力的因果关系,并进行异质性、基因多效性等敏感性分析探讨结果稳健性。运用Metaboanayst 5.0工具对具有潜在因果关系的代谢物进行代谢通路分析。结果与结论:①观察到124种代谢物和肌少症相关特征具有潜在因果关系(P<0.05);②甘露糖、1-花生四烯酸甘油磷酸胆碱与男性肌量增加存在显著因果关系(P<1.03×10^(-4));十五烷酸酯、甘氨酸分别与女性肌量、肌力下降存在显著因果关系(P<1.03×10^(-4));③代谢通路分析显示“乙醛酸和二羧酸代谢”“甘氨酸、丝氨酸和苏氨酸代谢”等8条代谢通路与肌少症的肌量、肌力水平改变相关;④鉴定出的血液代谢物可被视为临床实践中筛查和预防肌少症的有效循环代谢生物标志物,也可作为未来机制探索和药物靶点选择的候选分子。BACKGROUND:Clinical evidences have suggested a correlation between metabolic factors and sarcopenia.Blood metabolites have been found as biological factors underlying the mechanisms of musculoskeletal disorders.However,the causal relationship between blood metabolites and sarcopenia is unclear.OBJECTIVE:To explore the causal relationship between blood metabolites and sarcopenia-related traits through a two-sample Mendelian randomization analysis and to analyze their metabolic pathways.METHODS:A dataset of 486 blood metabolites and sarcopenia-related traits was obtained from public databases.The inverse variance weighting,MR-Egger and weighted median methods were used to assess the causal relationship of blood metabolites with muscle mass and strength across genders.Sensitivity analyses,including heterogeneity and gene pleiotropy,were performed to explore the robustness of the results.Metabolic pathway analysis of potential causal relationships was performed using the Metaboanayst 5.0 tool.RESULTS AND CONCLUSION:A total of 124 metabolites and sarcopenia-related traits were observed to have potential causal relationships(P<0.05).Mannose and 1-arachidonoylglycerophosphocholine were significantly causally associated with an increased muscle mass in males(P<1.03×10^(-4)).Pentadecanoate and glycine were significantly causally associated with decreased muscle mass and muscle strength in females,respectively(P<1.03×10^(-4)).Metabolic pathway analysis identified eight metabolic pathways associated with altered levels of muscle mass and muscle strength in sarcopenia,including the“glyoxylate and dicarboxylate metabolism”and“Glycine,serine and threonine metabolism.”The identified metabolites are considered as useful circulating metabolic biomarkers for screening and prevention of sarcopenia in clinical practice,serving as candidate molecules for future mechanistic exploration and drug target selection.

关 键 词：血液代谢物 肌少症 孟德尔随机化 代谢通路 因果关系 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R685