群体水平分析以确定驱动血浆代谢物谱变异的参数。
Population-Level Analysis to Determine Parameters That Drive Variation in the Plasma Metabolite Profiles.
作者信息
Al-Majdoub Mahmoud, Herzog Katharina, Daka Bledar, Magnusson Martin, Råstam Lennart, Lindblad Ulf, Spégel Peter
机构信息
Unit of Molecular Metabolism, Department of Clinical Sciences, Skåne University Hospital, Lund University, SE-205 02 Malmö, Sweden.
Centre for Analysis and Synthesis, Department of Chemistry, Lund University, 223 62 Lund, Sweden.
出版信息
Metabolites. 2018 Nov 15;8(4):78. doi: 10.3390/metabo8040078.
The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of flight mass spectrometry (QTOF-MS) to determine 106 metabolites in plasma samples from 2503 subjects in a cross-sectional study. We investigated the correlation structure of the metabolite profiles and generated uncorrelated metabolite factors using principal component analysis (PCA) and varimax rotation. Finally, we investigated associations between these factors and 34 clinical covariates. Our results suggest that liver function, followed by kidney function and insulin resistance show the strongest associations with the plasma metabolite profile. The association of specific phenotypes with several components may suggest multiple independent metabolic mechanisms, which is further supported by the composition of the associated factors.
血浆代谢组与多种表型和疾病相关。然而，尚未开展一项系统研究来探究控制代谢组的临床决定因素。因此，在本研究中，我们旨在确定血浆代谢物谱的主要决定因素。在一项横断面研究中，我们使用超高效液相色谱（UHPLC）与四极杆飞行时间质谱（QTOF-MS）联用，测定了2503名受试者血浆样本中的106种代谢物。我们研究了代谢物谱的相关结构，并使用主成分分析（PCA）和方差最大化旋转生成了不相关的代谢物因子。最后，我们研究了这些因子与34种临床协变量之间的关联。我们的结果表明，肝功能，其次是肾功能和胰岛素抵抗与血浆代谢物谱的关联最强。特定表型与多个组分的关联可能提示多种独立的代谢机制，相关因子的组成进一步支持了这一点。
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