Nonparametric Bayes Methods for Biomedical Studies

描述（由申请人提供）：我们建议开发新的统计方法，用于改善生物医学研究中多变量、纵向和功能数据的分析。人们越来越担心，在关键窗口期间发生的暴露可能导致以后的不良健康影响，促使进行前瞻性研究，收集关于多种随时间变化的暴露和健康结果的详细数据。需要新的统计方法来有效地发现这些高维数据集中的关键窗口和随时间变化的依赖关系，同时限制错误发现。这些方法可能导致对暴露引起不良健康影响的机制的根本性新见解，同时还允许制定有针对性的干预措施和更准确的疾病风险预测。我们的目标包括以下内容。1.开发非参数贝叶斯统计方法，以灵活地表征功能数据中个体之间的差异，例如氧化应激，生殖激素，营养素和妊娠体重随时间变化的轨迹。2.开发基于多个时变因素灵活预测健康反应的方法，同时估计关键窗口并发现不同因素之间的动态关系。3.应用这些方法来评估月经周期中氧化应激、营养素和生殖激素之间的关系，以解释年龄、肥胖和吸烟的作用。还考虑应用程序，以确定与短期婴儿健康结果相关的妊娠体重增加模式。公共卫生相关性：不良健康状况的发展，如不孕症和糖尿病，取决于遗传易感性和各种生活方式因素之间的相互作用，包括饮食和环境暴露。这些因素随年龄的变化是一个重要的风险决定因素，因为关键窗口可能在疾病发作前多年出现。我们提供必要的统计工具，以确定暴露的关键窗口，以便通过有针对性的干预措施降低风险。

DESCRIPTION (provided by applicant): We propose to develop new statistical methods for improving analyses of multivariate, longitudinal and functional data from biomedical studies. There is increasing concern that exposures occurring during critical windows can lead to later adverse health effects, motivating prospective studies collecting detailed data on multiple time-varying exposures and health outcomes. New statistical methods are needed to efficiently discover critical windows and time-varying dependencies in such high-dimensional data sets, while limiting false discoveries. These methods may lead to fundamental new insights into mechanisms by which exposures induce adverse health effects, while also allowing for the development of targeted interventions and more accurate predictions of disease risk. Our goals include the following. 1. Develop nonparametric Bayes statistical methods for flexibly characterizing differences among individuals in functional data, such as trajectories over time in oxidative stress, reproductive hormones, nutrients and pregnancy weight. 2. Develop methods for flexibly predicting a health response based on multiple time- varying factors, while also estimating critical windows and discovering dynamic relationships between the different factors. 3. Apply these methods to assess relationships between oxidative stress, nutrients and reproductive hormones over the menstrual cycle accounting for the role of age, obesity and smoking. Also consider applications to identify patterns of pregnancy weight gain associated with short-term infant health outcomes. PUBLIC HEALTH RELEVANCE: The development of adverse health conditions, such as infertility and diabetes, depends on the interaction between genetic predisposition and a variety of lifestyle factors, including diet and environmental exposures. Changes with age in these factors is an important determinate of risk, as critical windows can occur many years before disease onset. We provide the statistical tools necessary to identify critical windows of exposure in order to reduce risk through targeted interventions.