Application of an analytical framework for multivariate mediation analysis of environmental data.
Application of an analytical framework for multivariate mediation analysis of environmental data.
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DOI：
10.1038/s41467-020-19335-2
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发表时间：
2020-11-06
影响因子：
16.6
通讯作者：
Mukherjee B
中科院分区：
文献类型：
--
作者：
Aung MT;Song Y;Ferguson KK;Cantonwine DE;Zeng L;McElrath TF;Pennathur S;Meeker JD;Mukherjee B
环境毒物(邻苯二甲酸盐、苯酚、多环芳烃和金属)对妊娠结局的影响可能通过不同的毒理学机制进行调节。在这项研究中，我们引入了一个多变量中介分析的分析框架，以确定环境毒物(p = 38分析物)与分娩时孕周之间的中介途径(Q = 61介体)。我们的分析框架包括：(1)对独特的暴露-中介组合进行成对中介；(2)通过估计环境风险分数来降低暴露维度；(3)使用贝叶斯收缩中介分析、总体价值分解或中介路径惩罚进行多变量中介分析。降维表明，邻苯二甲酸盐风险分数每增加一个单位，分娩时(95%可信区间：0.48-1.67)的总效应为1.07孕周，细胞色素P450途径的二十烷类化合物介导了26%的效应(95%可信区间：4-63%)。细胞色素P450途径产生的二十烷类产物可能是邻苯二甲酸盐毒性的重要介体。不同的毒理学机制可能介导环境毒物对妊娠结局的影响。在这项研究中，作者引入了一个多变量中介分析的分析框架，以确定环境毒物与分娩时孕周之间的中介途径。
Diverse toxicological mechanisms may mediate the impact of environmental toxicants (phthalates, phenols, polycyclic aromatic hydrocarbons, and metals) on pregnancy outcomes. In this study, we introduce an analytical framework for multivariate mediation analysis to identify mediation pathways (q = 61 mediators) in the relationship between environmental toxicants (p = 38 analytes) and gestational age at delivery. Our analytical framework includes: (1) conducting pairwise mediation for unique exposure-mediator combinations, (2) exposure dimension reduction by estimating environmental risk scores, and (3) multivariate mediator analysis using either Bayesian shrinkage mediation analysis, population value decomposition, or mediation pathway penalization. Dimension reduction demonstrates that a one-unit increase in phthalate risk score is associated with a total effect of 1.07 lower gestational age (in weeks) at delivery (95% confidence interval: 0.48–1.67) and eicosanoids from the cytochrome p450 pathway mediated 26% of this effect (95% confidence interval: 4–63%). Eicosanoid products derived from the cytochrome p450 pathway may be important mediators of phthalate toxicity. Diverse toxicological mechanisms may mediate the impact of environmental toxicants on pregnancy outcomes. In this study the authors introduce an analytical framework for multivariate mediation analysis to identify mediation pathways in the relationship between environmental toxicants and gestational age at delivery.
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影响因子：
7.6
作者：
BARON, RM;KENNY, DA
通讯作者：
KENNY, DA
影响因子：
11.8
作者：
Ferguson, Kelly K.;McElrath, Thomas F.;Ko, Yi-An;Mukherjee, Bhramar;Meeker, John D.
通讯作者：
Meeker, John D.
影响因子：
5
作者：
Deng Y;Theken KN;Lee CR
通讯作者：
Lee CR
DOI：
10.1186/s12940-018-0400-3
发表时间：
2018-06-20
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Boss J;Zhai J;Aung MT;Ferguson KK;Johns LE;McElrath TF;Meeker JD;Mukherjee B
通讯作者：
Mukherjee B
影响因子：
3.8
作者：
Cooper, Beth W.;Cho, Taehyeon M.;Wallace, Andrew D.
通讯作者：
Wallace, Andrew D.