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），研究基因和环境在从青春期早期到成年中期物质使用障碍和共病问题纵向模式发展中的相互作用。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，来分析两项研究的数据，这些研究选择了不同的优势：一个家庭的全国概率样本（全国青年调查，博尔德科罗拉多大学行为科学研究所）和一个高风险的城市社区样本（西雅图社会发展项目，华盛顿大学社会发展研究组）。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，环境对物质使用、滥用和依赖以及犯罪发展的影响。这两项研究都包括DSM-IV诊断，以及其他药物滥用的分类和定量测量，以及相关的遗传表型。这两项研究的调查人员由行为遗传学研究所（科罗拉多大学博尔德分校）的成员加入，该研究所是美国行为遗传学研究的主要中心，他们与国家青年调查和其他国家健康和行为纵向研究的成功合作历史。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、血清素和药物代谢系统的遗传多态性有关。拟议的研究将(1)收集SSDP和NYS的血液样本，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覆盖对现有和新DNA样本进行基因分型；(3)研究基因-环境在SUD发展和合并症中的相互作用。

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.