论文标题
将生物学知识整合在基于内核的环境混合物和健康分析中
Integrating Biological Knowledge in Kernel-Based Analyses of Environmental Mixtures and Health
论文作者
论文摘要
环境健康研究的一个关键目标是评估污染物混合物带来的风险。由于混合物的流行病学研究可能很昂贵,因此研究人员应该将有关混合物的先验知识纳入其分析中。这项工作扩展了贝叶斯多指数模型(BMIM),该模型假设曝光响应函数是一组具有一组暴露特定权重的污染物的线性组合的非参数函数。该框架很有吸引力,因为它结合了响应表面方法的灵活性与线性索引模型的解释性。我们提出了三种策略,将毒理学知识纳入BMIM中的指标构建:(a)限制指数权重,(b)通过暴露转化来构造指数权重,以及(c)在指数权重上放置信息的先验。我们提出了一种新的先前规范,该规范将基于通常来自以前的毒理学研究得出的相对效能因子的相对效能因子结合了尖峰和slab变量的选择和信息性的差异分布。在模拟中,我们表明,当事先信息正确时,提议的先验者会改善推论,并且在事先信息不正确时可以防止幼稚毒理学模型所遭受的错误指定。此外,不同的策略可能会混合使用,以适合不同的索引以适合可用信息(或缺乏信息)。我们证明了对来自国家健康和营养检查调查数据分析的分析的拟议方法,并纳入了文献中可用的有毒等效因素获得的相对化学效力的先前信息。
A key goal of environmental health research is to assess the risk posed by mixtures of pollutants. As epidemiologic studies of mixtures can be expensive to conduct, it behooves researchers to incorporate prior knowledge about mixtures into their analyses. This work extends the Bayesian multiple index model (BMIM), which assumes the exposure-response function is a non-parametric function of a set of linear combinations of pollutants formed with a set of exposure-specific weights. The framework is attractive because it combines the flexibility of response-surface methods with the interpretability of linear index models. We propose three strategies to incorporate prior toxicological knowledge into construction of indices in a BMIM: (a) constraining index weights, (b) structuring index weights by exposure transformations, and (c) placing informative priors on the index weights. We propose a novel prior specification that combines spike-and-slab variable selection with informative Dirichlet distribution based on relative potency factors often derived from previous toxicological studies. In simulations we show that the proposed priors improve inferences when prior information is correct and can protect against misspecification suffered by naive toxicological models when prior information is incorrect. Moreover, different strategies may be mixed-and-matched for different indices to suit available information (or lack thereof). We demonstrate the proposed methods on an analysis of data from the National Health and Nutrition Examination Survey and incorporate prior information on relative chemical potencies obtained from toxic equivalency factors available in the literature.