Bayesian Methods for High-Dimensional Epidemiologic Data

描述（由申请人提供）：我们开发了新的统计技术，用于高维协变量数据的非参数贝叶斯分析，直接受到有史以来对出生缺陷原因进行的最大规模基于人群的研究的激励。我们开发的方法将能够在高维环境，生物医学，药理学和社会人口学风险因素（以及它们之间的相互作用）以及众多出生缺陷中借用信息和收缩，其中许多缺陷太罕见而无法单独研究。使用由胚胎发育直接驱动的等级结构，信息的借用可以通过我们对胚胎机械发育的知识来告知。这些新方法可能会对罕见先天性畸形的研究产生重大影响。待开发的方法在公共卫生和医学中具有广泛的应用，其中所关注的暴露或特征可能数量很大，并且相互作用很重要，例如通过环境和基因-基因相互作用检查高维基因。 公共卫生相关性：该项目利用有史以来对出生缺陷原因进行的最大规模基于人群的研究数据，解决了寻找先天性畸形病因和发病机制线索的迫切需要。虽然出生缺陷是婴儿死亡的主要原因，是1-4岁儿童死亡的主要原因，也是美国过早死亡的第五大原因，但许多个体缺陷太罕见，无法进行全面研究，即使是在非常大的研究中。我们的新的稀疏收缩统计方法结合了胚胎发育的现有知识，并允许在不同的出生缺陷之间借用一些信息，同时将每个缺陷作为统计模型中的独立实体。这些新方法将使研究人员能够调查多重暴露和暴露组合对多种结果的同时影响。

DESCRIPTION (provided by applicant): We develop novel statistical techniques for nonparametric Bayes analysis of high-dimensional covariate data, directly motivated by the largest population-based study ever conducted on the causes of birth defects. The methods we develop will enable borrowing of information and shrinkage across high-dimensional environmental, biomedical, pharmacological, and sociodemographic risk factors (and interactions among them) and across a multitude of birth defects, many of which are too rare to be studied in isolation. Using a hierarchical structure directly motivated by embryonic development, the borrowing of information can be informed by our knowledge of mechanistic development of the embryo. These novel methods may significantly impact the study of rare congenital malformations. The methods to be developed have broad application in public health and medicine, where exposures or characteristics of interest may be great in number and interactions are important, such as the examination high-dimensional gene by environment and gene-gene interactions. PUBLIC HEALTH RELEVANCE: This project addresses a critical need of finding clues to the etiology and pathogenesis of congenital mal- formations, using data from the largest population-based study ever conducted on the causes of birth defects. While birth defects are the leading cause of infant mortality, the leading cause of death among children aged 1-4, and the fifth-ranked cause of premature mortality in the United States, many individual defects are too rare to be studied comprehensively, even in studies that are very large. Our new statistical methods for sparse shrinkage incorporate current knowledge of embryonic development and allow some borrowing of information across differ- ent birth defects while keeping each defect as a separate entity of interest in the statistical model. These novel methods will allow investigators to investigate the simultaneous influence of multiple exposures and combinations of exposures on multiple outcomes.