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Abstract：
BACKGROUND: Sarcopenia is a progressive loss of muscle mass and function. Since skeletal muscle plays a critical role in metabolic homeostasis, identifying the relationship of blood metabolites with sarcopenia components would help understand the etiology of sarcopenia.
METHODS: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed.
RESULTS: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10- 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses.
CONCLUSIONS: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health.
METHODS: A two-sample Mendelian randomization study was conducted to examine the causal relationship of blood metabolites with the components of sarcopenia. Summary genetic association data for 309 known metabolites were obtained from the Twins UK cohort and KORA F4 study (7824 participants). The summary statistics for sarcopenia components [hand grip strength (HGS), walking pace (WP), and appendicular lean mass (ALM)] were obtained from the IEU Open GWAS project (461,089 participants). The inverse variance weighted method was used, and the MR-Egger, weighted median, and MR-PRESSO were used for the sensitivity analyses. Metabolic pathways analysis was further performed.
RESULTS: Fifty-four metabolites associated with sarcopenia components were selected from 275 known metabolites pool. Metabolites that are causally linked to the sarcopenia components were mainly enriched in amino sugar and nucleotide sugar metabolism, galactose metabolism, fructose and mannose metabolism, carnitine synthesis, and biotin metabolism. The associations of pentadecanoate (15:0) with ALM, and 3-dehydrocarnitine and isovalerylcarnitine with HGS were significant after Bonferroni correction with a threshold of P < 1.82 × 10- 4 (0.05/275). Meanwhile, the association of hyodeoxycholate and glycine with the right HGS, and androsterone sulfate with ALM were significant in the sensitivity analyses.
CONCLUSIONS: Blood metabolites from different metabolism pathways were causally related to the components of sarcopenia. These findings might benefit the understanding of the biological mechanisms of sarcopenia and targeted drugs development for muscle health.
摘要：
背景：肌肉减少症是肌肉质量和功能的进行性丧失。由于骨骼肌在代谢稳态中起关键作用，确定血液代谢产物与肌肉减少症成分的关系将有助于了解肌肉减少症的病因。
方法：进行了两个样本的孟德尔随机研究，以检查血液代谢物与肌肉减少症成分的因果关系。309种已知代谢物的汇总遗传关联数据来自英国双胞胎队列和KORAF4研究(7824名参与者)。肌肉减少症成分的统计摘要[手握力（HGS），步行速度（WP），和阑尾瘦体重（ALM）]从IEUOpenGWAS项目（461,089名参与者）获得。采用逆方差加权法，和MR-Egger，加权中位数，和MR-PRESSO用于敏感性分析。进一步进行代谢途径分析。
结果：从275种已知的代谢产物库中选择了54种与肌肉减少症成分相关的代谢产物。与肌肉减少症成分有因果关系的代谢物主要富含氨基糖和核苷酸糖代谢，半乳糖代谢，果糖和甘露糖代谢，肉碱合成，和生物素代谢。十五烷酸（15：0）与ALM的关联，Bonferroni校正后，3-脱氢肉碱和异戊酰基肉碱与HGS的阈值为P<1.82×10-4（0.05/275）。同时,猪去氧胆酸盐和甘氨酸与正确的HGS的关联，和硫酸雄酮与ALM在敏感性分析中具有显著意义。
结论：来自不同代谢途径的血液代谢产物与肌少症的成分有因果关系。这些发现可能有助于了解肌肉减少症的生物学机制和肌肉健康的靶向药物开发。
方法：进行了两个样本的孟德尔随机研究，以检查血液代谢物与肌肉减少症成分的因果关系。309种已知代谢物的汇总遗传关联数据来自英国双胞胎队列和KORAF4研究(7824名参与者)。肌肉减少症成分的统计摘要[手握力（HGS），步行速度（WP），和阑尾瘦体重（ALM）]从IEUOpenGWAS项目（461,089名参与者）获得。采用逆方差加权法，和MR-Egger，加权中位数，和MR-PRESSO用于敏感性分析。进一步进行代谢途径分析。
结果：从275种已知的代谢产物库中选择了54种与肌肉减少症成分相关的代谢产物。与肌肉减少症成分有因果关系的代谢物主要富含氨基糖和核苷酸糖代谢，半乳糖代谢，果糖和甘露糖代谢，肉碱合成，和生物素代谢。十五烷酸（15：0）与ALM的关联，Bonferroni校正后，3-脱氢肉碱和异戊酰基肉碱与HGS的阈值为P<1.82×10-4（0.05/275）。同时,猪去氧胆酸盐和甘氨酸与正确的HGS的关联，和硫酸雄酮与ALM在敏感性分析中具有显著意义。
结论：来自不同代谢途径的血液代谢产物与肌少症的成分有因果关系。这些发现可能有助于了解肌肉减少症的生物学机制和肌肉健康的靶向药物开发。
