Integrating Genes, Environment, & Development in the Etiology of Substance Abuse

整合基因、环境、

基本信息

批准号：
8477159
负责人：
BRIAN M HICKS
金额：
$ 18.14万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8477159
关键词：
Adolescence Age Alcohol or Other Drugs use Alcohols Alleles Award Behavior Behavioral Genetics Bioinformatics Candidate Disease Gene Chronic Disease Complex Consult Custom Data Dependence Development Developmental Process Diagnostic Diagnostic and Statistical Manual Economics Environment Environmental Exposure Environmental Risk Factor Epidemiology Etiology Exposure to Failure Family Family Study Genes Genetic Genetic Markers Genetic Polymorphism Genetic Predisposition to Disease Genetic Research Genotype Goals Health Health Care Costs Heritability Human Human Genome Intervention Light Longitudinal Studies Measures Mentors Methodology Methods Minnesota Molecular Outcome Participant Persons Phenotype Prevention Preventive Intervention Principal Investigator Process Productivity Psychiatry Psychometrics Public Health Quality Control Rehabilitation therapy Research Research Personnel Risk Risk Factors Role Sampling Scanning Smoker Substance Use Disorder Substance abuse problem Symptoms System Techniques Time Training Twin Multiple Birth Universities Variant Victimization Violence Youth addiction adolescent drug abuse base career design drug abuse education drug abuser effective therapy emerging adult experience follow-up genetic association genetic risk factor genome wide association study high risk improved indexing insight novel novel strategies programs skills sound

项目摘要

DESCRIPTION (provided by applicant): The overarching goals of this proposal are twofold: 1) to support the candidate in gaining additional training in the use of molecular and statistical genetic methods to identify risk alleles for substance use disorders (SUD), and 2) conduct a genome wide association study (GWAS) for a novel phenotype, a pre-morbid liability index for SUDs, and replication studies in two independent samples. The advantage of focusing on indicators of pre-morbid risk (i.e. prior to initiation of substance use) is that analyses are based on underlying rather than expressed risk and so may provide a more sensitive measure of genetic liability than manifest or "post-morbid" measures of SUDs. Focusing on pre-morbid liability also provides a sound theoretical framework to examine developmental processes associated with the emergence of SUDs such as exposure to environmental risk (gene-environment correlations) and sensitivity to environmental adversity (gene x environment interactions). The training portion of the proposal focuses on gaining skills in bioinformatics to identify candidate gene systems and select informative polymorphisms (e.g. SNPs) as well as expertise in statistical analyses to detect associations between genetic markers and complex phenotypes such as SUDs. The research plan entails conducting a GWAS of 61 OK SNPs on a measure of pre-morbid liability to SUDs on approximately 6000 participants. Replication studies of significant findings from the GWAS will then be conducted in two independent samples of high-risk youth. The research plan also includes studies examining mechanisms of G-E interplay that underlie the development of SUDs by utilizing a longitudinal twin design. The award will also assist the candidate in pursuing his long-term goal of becoming an independent researcher and is likely to yield important insights into the etiology of SUDs. PUBLIC HEALTH RELEVANCE: We propose a novel approach to identifying genes associated with substance abuse by focusing on risk factors present prior to initiation of substance use. Pooling multiple longitudinal samples (N~6000), we will conduct a genome wide association study on a novel measure of pre-morbid risk for substance abuse to identify specific risk genes.

描述（由申请人提供）：该提案的总体目标是双重的：1）支持候选人在使用分子和统计遗传学方法方面获得额外的培训，以识别物质使用障碍（SUD）的风险等位基因（SUD）和2）进行基因组广泛的关联研究（GWAS），以进行新的现象类型，以进行新的现象，并进行预先识别索引，并进行两次索引，并进行两次索引，并进行了两次索引，并进行了两次索引。专注于早期风险指标（即在开始使用物质之前）的优势在于，分析是基于潜在的而不是表达的风险，因此可能提供对遗传责任的衡量标准，而不是明显的或“后爆发后”的SUD措施。专注于早期责任的还提供了一个合理的理论框架，以检查与SUD的出现相关的发育过程，例如暴露于环境风险（基因 - 环境相关性）和对环境逆境（Gene X环境相互作用）的敏感性。该提案的培训部分着重于获得生物信息学的技能，以鉴定候选基因系统并选择信息性的多态性（例如SNP）以及统计分析的专业知识，以检测遗传标记和复杂表型之间的关联。该研究计划需要对大约6000名参与者的SUD进行量度的GWAS进行61个OK SNP。然后将在两个高风险青年的独立样本中对GWAS的重大发现进行复制研究。该研究计划还包括研究G-E相互作用的机制，这些机制是通过使用纵向双胞胎设计来发展SUD的基础的。该奖项还将帮助候选人追求成为独立研究人员的长期目标，并可能对SUD的病因产生重要的见解。公共卫生相关性：我们提出了一种新颖的方法来识别与药物滥用相关的基因，通过重点关注使用物质使用之前存在的危险因素。汇集了多个纵向样本（n〜6000），我们将对对滥用药物滥用的新型风险的新量度进行基因组广泛的关联研究，以识别特定的风险基因。