Statistical Modeling and Genetic Epidemiology of Dental Caries in GWAS Analysis

GWAS 分析中龋齿的统计模型和遗传流行病学

• 批准号: 8028424
• 负责人: Xiaojing Wang
• 金额: $ 22.73万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8028424
• 关键词: Accounting; Adult; Affect; Age; Area; Behavior; Child; Chromosome Mapping; Chronic Disease; Complex; Data; Data Set; Dental caries; Development; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Equation; Etiology; Future; Genes; Genetic; Genetic Risk; Genome Scan; Genotype; Goals; Hand; Heritability; Human; Lead; Measurement; Measures; Methods; Mixed Dentition; Modeling; Phenotype; Prevention; Prevention strategy; Primary Dentition; Property; Risk; Severities; Side; Simulate; Statistical Distributions; Statistical Methods; Statistical Models; Testing; Work; Writing; endophenotype; epidemiology study; genetic analysis; genetic epidemiology; genetic risk factor; genome wide association study; genome-wide; improved; infancy; innovation; insight; non-genetic; novel strategies; permanent tooth; simulation; tool; tooth surface; treatment strategy

DESCRIPTION (provided by applicant): Dental caries, a multifactorial complex disease, remains the one of the most common chronic disease of human beings. The etiology of dental caries has been studied extensively, and both environmental and genetic factors have been implicated in caries risk. Our long-term goal is to improve understanding of the mechanism leading to dental caries development in both children and adults by uncovering underlying genetic risk factors that alone or through interaction with environmental factors, increase caries risk, thus informing new strategies for prevention and treatment. The objective of this application, which is the next step in pursuit of that goal, is to develop and test new approaches for modeling dental caries in genetic epidemiology studies, and then to apply those approaches to better understand the interaction between genetic and environmental risk factors using a large existing genome-wide dataset. In Aim 1 we will study epidemiological properties, heritabilities, and modeling strategies for various caries phenotypes, and in Aim 2 we will look at the power of different gene x environment modeling strategies in the context of whole-genome scanning. The successful completion of Aims 1 and 2 will provide critical statistical and epidemiological tools for current and future studies of the genetic epidemiology of dental caries. In Aim 3 we will apply the best approaches from Aims 1 and 2 to several existing GWAS caries datasets to identify and understand genetic and environmental risk factors that affect caries risk. The successful completion of Aim 3 will lead to new discoveries about the etiology of caries, and in particular about the gene x environment interactions that differentially affect risk in primary, permanent, and mixed dentition. This better understanding will eventually lead to better prevention and treatment. PUBLIC HEALTH RELEVANCE: Dental caries, a multifactorial complex disease, remains the one of the most common chronic diseases of human beings. We propose to compare and evaluate a variety of caries modeling strategies for identifying genetic and environmental risk factors and their interactions. The successful completion of this project will eventually lead to better understanding of the etiology, prevention and even the customized treatment strategies of caries.

描述（申请人提供）：龋齿是一种多因素的复杂疾病，是人类最常见的慢性疾病之一。龋齿的病因学已被广泛研究，环境和遗传因素都与龋齿风险有关。我们的长期目标是通过发现单独或通过与环境因素相互作用增加龋齿风险的潜在遗传风险因素，从而提高对儿童和成人龋齿发展机制的理解，从而为预防和治疗提供新的策略。本应用程序的目标是开发和测试在遗传流行病学研究中模拟龋齿的新方法，然后使用现有的大型全基因组数据集应用这些方法来更好地理解遗传和环境风险因素之间的相互作用。在目标1中，我们将研究各种龋表型的流行病学特性，遗传性和建模策略，在目标2中，我们将研究在全基因组扫描背景下不同基因x环境建模策略的能力。目标1和目标2的成功完成将为当前和未来的龋齿遗传流行病学研究提供关键的统计和流行病学工具。在目标3中，我们将把目标1和目标2中的最佳方法应用于几个现有的GWAS龋齿数据集，以识别和理解影响龋齿风险的遗传和环境风险因素。Aim 3的成功完成将导致龋齿病因学的新发现，特别是基因与环境的相互作用对原发性、永久性和混合牙列的风险有不同的影响。这种更好的理解最终将导致更好的预防和治疗。