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

描述(由申请人提供)：本提案响应了基因、环境和发展倡议(RFA-DA-07-012)，旨在研究从青春期早期到成年中期药物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，其中包括行为、分子和统计遗传学、人类发育、社会学、心理学以及物质使用障碍和犯罪的发展方面的专家，以分析来自两项不同优势的研究的数据：全国家庭概率样本(国家青年调查，科罗拉多大学博尔德大学行为科学研究所)和高危城市社区样本(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多年的纵向数据，说明从青春期早期到成年中期，环境对药物使用、滥用和依赖以及青少年犯罪发展的影响。这两项研究都包括DSM-IV诊断，以及物质滥用的其他分类和定量测量以及已证明的遗传性的相关表型。这两项研究的研究人员还有行为遗传学研究所(科罗拉多大学博尔德分校)的成员，该研究所是美国领先的行为遗传学研究中心，曾与全国青年调查和其他全国性的健康和行为纵向研究成功合作。物质使用障碍的发展与家庭、同伴、学校和社区在一生中的预测因素有关，也与多巴胺、5-羟色胺和药物代谢系统的遗传多态有关。这项拟议的研究将(1)从SSDP和NYS收集血液样本，为NIDA遗传学联盟以及这两项研究提供DNA数据；(2)利用目标基因的密集SNP覆盖对现有的和新的DNA样本进行基因分型；以及(3)检查在SUD和共病问题的发展中基因-环境的相互作用。

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.