Bobb Jennifer F, Valeri Linda, Claus Henn Birgit, Christiani David C, Wright Robert O, Mazumdar Maitreyi, Godleski John J, Coull Brent A
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
Biostatistics. 2015 Jul;16(3):493-508. doi: 10.1093/biostatistics/kxu058. Epub 2014 Dec 22.
Because humans are invariably exposed to complex chemical mixtures, estimating the health effects of multi-pollutant exposures is of critical concern in environmental epidemiology, and to regulatory agencies such as the U.S. Environmental Protection Agency. However, most health effects studies focus on single agents or consider simple two-way interaction models, in part because we lack the statistical methodology to more realistically capture the complexity of mixed exposures. We introduce Bayesian kernel machine regression (BKMR) as a new approach to study mixtures, in which the health outcome is regressed on a flexible function of the mixture (e.g. air pollution or toxic waste) components that is specified using a kernel function. In high-dimensional settings, a novel hierarchical variable selection approach is incorporated to identify important mixture components and account for the correlated structure of the mixture. Simulation studies demonstrate the success of BKMR in estimating the exposure-response function and in identifying the individual components of the mixture responsible for health effects. We demonstrate the features of the method through epidemiology and toxicology applications.
由于人类始终暴露于复杂的化学混合物中,因此评估多种污染物暴露对健康的影响是环境流行病学以及美国环境保护局等监管机构极为关注的问题。然而,大多数健康影响研究都集中在单一因素上,或者考虑简单的双向相互作用模型,部分原因是我们缺乏能够更现实地捕捉混合暴露复杂性的统计方法。我们引入贝叶斯核机器回归(BKMR)作为一种研究混合物的新方法,其中健康结果基于混合物(如空气污染或有毒废物)成分的灵活函数进行回归,该函数通过核函数指定。在高维环境中,采用了一种新颖的分层变量选择方法来识别重要的混合物成分,并考虑混合物的相关结构。模拟研究证明了BKMR在估计暴露-反应函数以及识别对健康影响负责的混合物单个成分方面的成功。我们通过流行病学和毒理学应用展示了该方法的特点。