Genetic/Epigenetic Markers, Social Contexts, Lifecourse and Risky Health Behavior

遗传/表观遗传标记、社会背景、生命历程和危险健康行为

• 批准号: 7938632
• 负责人: Guang Guo
• 金额: $ 49.99万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938632
• 关键词: Address; Admixture; Adolescent; Agaricales; Area; Behavior; Behavioral; Biocompatible Materials; Cells; Complex; Consensus; DNA; Data; Data Set; Databases; Detection; Development; Dimensions; Disease; Drug usage; Environment; Environmental Risk Factor; Epigenetic Process; Evaluation; Frequencies; Friends; Future; Genes; Genetic; Genetic Polymorphism; Genomics; Goals; Health; Health behavior; Heroin; Heterogeneity; Human; Ice; Immunoprecipitation; Individual; Investigation; Life Cycle Stages; Link; Longitudinal Studies; Marijuana Smoking; Measures; Methods; Methylation; Modeling; Neighborhoods; Oligonucleotide Microarrays; Pattern; Phenotype; Physical environment; Pilot Projects; Population; Prevention; Principal Component Analysis; Procedures; Publishing; Research Personnel; Risk Behaviors; Saliva; Sample Size; Sampling; Scanning; Schools; Sexual Partners; Siblings; Smoking; Social Behavior; Social Environment; Social Network; Social Sciences; Source; Speed; Staging; Statistical Methods; Statistical Models; Stratification; Structure; Study Subject; Substance abuse problem; T-Lymphocyte; Testing; Universities; abstracting; analytical method; base; behavior influence; binge drinking; brain tissue; cocaine use; contextual factors; critical developmental period; density; design; drinking; ecstasy; gene environment interaction; genetic variant; genome wide association study; microbial; novel; novel strategies; peer; peripheral blood; pill; public health relevance; response; simulation; social; trait

DESCRIPTION (provided by applicant): Genetic/Epigenetic Markers, Social Contexts, Lifecourse & Risky Health Behaviors PROJECT SUMMARY/ABSTRACT This application addresses broad challenge area (01) Behavior, Behavioral Change, and Prevention and two highly related specific Challenge Topics: (A) 01-OD(OBSSR)-102* Methods for studying the interactions among behaviors, environments, and genetic/epigenetic processes and (B) 01-DA-111: Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods. The first specific topic of 01-OD(OBSSR)- 102 emphasizes the development of analytical methods in this area and the second topic of 01-DA-111 emphasizes the actual integration of environmental and developmental variables with genotypic information in order to permit comprehensive model-building and hypothesis testing for determining genetic, environmental, and developmental contributions to substance abuse and related phenotypes. The overall challenge for our application is to integrate genetic polymorphisms, epigenetic markers, social contextual measures, and developmental periods into analysis of risky health behaviors. The past 2-3 years saw an unparalleled succession of discoveries in the genomics of complex diseases. So far, GWAS has focused on estimating genetic main effects. However, the general consensus is that the links between genetic heritage and complex human traits, especially human behaviors, are enormously complicated, typically involving multiple genes, epigenetic markers, social contextual factors, life course stages, and the interactions among these sources. In this application, we propose three goals in response to the overall challenge. First, we propose two novel analytical approaches for addressing the issue of high-dimension-low-sample-size (HDLSS) or too many independent variables for the available sample size, which is one of the most difficult issues in genetic studies of complex human traits. These are the method of variable selection under HDLSS and the method of simultaneous selection of important variables and stratification of subjects. Both methods are for estimating genetic main effects and gene-environment interaction effects. Our second goal is to actually integrate genetic data (an Illumina GoldenGate array of 1536 SNPs), social contextual data, and life course into investigations of the causes of nine most common risky health behaviors (marijuana use, cocaine use, other illegal drug use, number of sexual partners, binge drinking, drinking quantity, smoking quantity, smoking frequency, and seatbelt non-wearing), drawing data (N=2,600) from the National Longitudinal Study of Adolescent Health. Our Third Goal is to carry out a pilot project that investigates the feasibility of saliva DNA for a population-level methylation study. The pilot project addresses several technical issues, which must be resolved before a large- scale population methylation study via saliva DNA can be implemented - the issues of cellular heterogeneity or cell identity, potential contamination of saliva by orally ingested agents, and the detection of informative methylation pattern differences in T cells from Saliva. 1 Genetic/Epigenetic Markers, Social Contexts, Lifecourse & Risky Health Behaviors Public Health Relevance - The overall challenge for our application is to integrate genetic polymorphisms, epigenetic markers, social contextual measures, and developmental periods into analysis of risky health behaviors. This application explores two novel statistical methods designed to address the integration, performs the integrated analysis using Add Health data, and conducts a pilot study investigating the feasibility of using saliva DNA for a large scale epigenetic project.

描述（由申请人提供）：遗传/表观遗传标记、社会背景、生命历程和危险健康行为 项目摘要/摘要 本申请解决了广泛的挑战领域 (01) 行为、行为改变和预防以及两个高度相关的具体挑战主题：(A ) 01-OD(OBSSR)-102* 研究行为、环境和遗传/表观遗传过程之间相互作用的方法和 (B) 01-DA-111：研究关键发育时期个体行为、社会和物理环境以及遗传/表观遗传过程之间相互作用的方法。 01-OD(OBSSR)-102 的第一个具体主题强调该领域分析方法的发展，01-DA-111 的第二个主题强调环境和发育变量与基因型信息的实际整合，以便建立综合模型-建立和假设检验以确定遗传、环境和发育对药物滥用和相关表型的贡献。我们应用的总体挑战是将遗传多态性、表观遗传标记、社会背景测量和发育时期整合到危险健康行为的分析中。过去的两三年里，复杂疾病的基因组学领域取得了前所未有的一系列发现。到目前为止，GWAS 的重点是估计遗传主效应。然而，普遍的共识是，遗传遗产与复杂的人类特征（尤其是人类行为）之间的联系非常复杂，通常涉及多个基因、表观遗传标记、社会背景因素、生命历程阶段以及这些来源之间的相互作用。在此应用中，我们提出了三个目标来应对总体挑战。首先，我们提出了两种新颖的分析方法来解决高维低样本量（HDLSS）或可用样本量的自变量过多的问题，这是复杂人类遗传研究中最困难的问题之一特征。这些是HDLSS下的变量选择方法和同时选择重要变量和受试者分层的方法。两种方法都用于估计遗传主效应和基因-环境相互作用效应。我们的第二个目标是真正将遗传数据（包含 1536 个 SNP 的 Illumina GoldenGate 阵列）、社会背景数据和生命历程整合到九种最常见的危险健康行为（大麻使用、可卡因使用、其他非法药物使用、性伴侣数量、酗酒、饮酒量、吸烟量、吸烟频率、不系安全带），数据来自全国纵向研究（N=2,600）青少年健康。我们的第三个目标是开展一个试点项目，调查唾液 DNA 用于人群水平甲基化研究的可行性。该试点项目解决了几个技术问题，这些问题必须在通过唾液 DNA 进行大规模群体甲基化研究之前得到解决，包括细胞异质性或细胞身份问题、口服制剂对唾液的潜在污染以及信息检测等问题。唾液 T 细胞的甲基化模式差异。 1 遗传/表观遗传标记、社会背景、生命历程和危险健康行为公共卫生相关性 - 我们应用的总体挑战是将遗传多态性、表观遗传标记、社会背景测量和发育时期整合到危险健康行为的分析中。该应用程序探索了两种旨在解决整合问题的新颖统计方法，使用 Add Health 数据执行整合分析，并进行了一项试点研究，调查使用唾液 DNA 进行大规模表观遗传项目的可行性。