Gene-Environment Interplay in the Development of Drug Abuse and Comorbid Problems

描述（由申请人提供）：本提案响应基因、环境和发展倡议（RFA-DA-07-012），以检查从青春期早期到成年中期的物质使用障碍和共病问题的纵向模式发展中基因和环境的相互作用。为此，我们组建了一个跨学科团队，包括行为，分子和统计遗传学，人类发展，社会学，心理学以及物质使用障碍和犯罪发展方面的专家，以分析两项针对不同优势选择的研究的数据：全国家庭概率抽样（国家青年调查，行为科学研究所，科罗拉多大学，博尔德）和一个高风险的城市社区样本（西雅图社会发展项目，社会发展研究小组，华盛顿大学）。每项研究都提供了20多年来关于环境对从青春期早期到成年中期的药物使用、滥用和依赖以及犯罪发展的影响的纵向数据。这两项研究都包括DSM-IV诊断以及其他药物滥用和相关遗传表型的分类和定量测量。这两项研究的调查人员加入了行为遗传学研究所（科罗拉多大学，博尔德）的成员，该研究所是美国行为遗传学研究的领先中心，他们与全国青年调查和其他国家健康和行为纵向研究有着成功的合作历史。物质使用障碍的发展与生命过程中的家庭、同伴、学校和社区预测因素有关，也与多巴胺、5-羟色胺和药物代谢系统的遗传多态性有关。拟议的研究将（1）从SSDP和NYS收集血液样本，为NIDA遗传学联盟以及两项研究提供DNA数据;（2）使用靶基因的密集SNP覆盖对现有和新的DNA样本进行基因分型;（3）检查SUD发展中的基因-环境相互作用和共病问题。

DESCRIPTION (provided by applicant): This proposal responds to the Genes, Environment, and Development Initiative (RFA-DA-07-012) to examine the interplay of genes and environment in the development of longitudinal patterns of substance use disorders and comorbid problems from early adolescence through mid-adulthood. To this end, we have assembled an interdisciplinary team including specialists in behavioral, molecular, and statistical genetics, human development, sociology, psychology, and the development of substance use disorders and delinquency, to analyze data from two studies selected for different strengths: a national probability sample of households (National Youth Survey, Institute of Behavioral Science, University of Colorado, Boulder) and a high-risk urban community sample (Seattle Social Development Project, Social Development Research Group, University of Washington). Each study provides over 20 years of longitudinal data on environmental influences on the development of substance use, abuse and dependence, and delinquency from early adolescence to mid-adulthood. Both studies include DSM-IV diagnoses as well as other categorical and quantitative measures of substance abuse and related phenotypes of demonstrated heritability. Investigators on these two studies are joined by members of the Institute for Behavioral Genetics (University of Colorado, Boulder), a leading center for behavioral genetic studies in the US, who have a history of successful collaboration with the National Youth Survey and other national longitudinal studies of health and behavior. The development of substance use disorders has been associated with family, peer, school and community predictors during the life course, as well as with genetic polymorphisms in the dopamine, serotonin and drug metabolism systems. The proposed study will (1) collect blood samples from both SSDP and NYS to provide DNA data to the NIDA genetics consortium as well as to the two studies; (2) genotype existing and new DNA samples using dense SNP coverage of targeted genes; and (3) examine the gene-environment interplay in the development of SUD and comorbid problems.