Bessonneau Vincent, Gerona Roy R, Trowbridge Jessica, Grashow Rachel, Lin Thomas, Buren Heather, Morello-Frosch Rachel, Rudel Ruthann A
Silent Spring Institute, 320 Nevada Street, Newton, MA, 02460, USA.
Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement Et Travail) - UMR_S 1085, Univ. Rennes, 35000, Rennes, France.
Sci Rep. 2021 Apr 7;11(1):7607. doi: 10.1038/s41598-021-87070-9.
Given the complex exposures from both exogenous and endogenous sources that an individual experiences during life, exposome-wide association studies that interrogate levels of small molecules in biospecimens have been proposed for discovering causes of chronic diseases. We conducted a study to explore associations between environmental chemicals and endogenous molecules using Gaussian graphical models (GGMs) of non-targeted metabolomics data measured in a cohort of California women firefighters and office workers. GGMs revealed many exposure-metabolite associations, including that exposures to mono-hydroxyisononyl phthalate, ethyl paraben and 4-ethylbenzoic acid were associated with metabolites involved in steroid hormone biosynthesis, and perfluoroalkyl substances were linked to bile acids-hormones that regulate cholesterol and glucose metabolism-and inflammatory signaling molecules. Some hypotheses generated from these findings were confirmed by analysis of data from the National Health and Nutrition Examination Survey. Taken together, our findings demonstrate a novel approach to discovering associations between chemical exposures and biological processes of potential relevance for disease causation.
鉴于个体在生命过程中会经历来自外源性和内源性的复杂暴露，有人提出进行全暴露组关联研究，以检测生物样本中小分子的水平，从而发现慢性病的病因。我们开展了一项研究，利用在一组加利福尼亚州女消防员和办公室工作人员中测量的非靶向代谢组学数据的高斯图形模型（GGM），来探索环境化学物质与内源性分子之间的关联。GGM揭示了许多暴露-代谢物关联，包括接触单羟基异壬基邻苯二甲酸酯、对羟基苯甲酸乙酯和4-乙基苯甲酸与参与类固醇激素生物合成的代谢物有关，全氟烷基物质与调节胆固醇和葡萄糖代谢的胆汁酸-激素以及炎症信号分子有关。通过对美国国家健康与营养检查调查的数据进行分析，证实了从这些发现中得出的一些假设。综合来看，我们的研究结果展示了一种新方法，用于发现化学暴露与可能与疾病因果关系相关的生物过程之间的关联。
