Genetics of Adolescent Antisocial Drug Dependence

青少年反社会药物依赖的遗传学

• 批准号: 8212296
• 负责人: TAMARA L WALL
• 金额: $ 39.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8212296
• 关键词: Address; Adolescence; Adolescent; Affect; Agreement; Behavior; Behavioral; Candidate Disease Gene; Clinical; Collaborations; Communities; Comorbidity; Conduct Disorder; DNA; Data; Data Set; Databases; Development; Drug Addiction; Drug abuse; Elements; Family; Genetic; Genotype; Guidelines; Health; Individual; Maps; Molecular; National Institute of Drug Abuse; Neurobiology; Pattern; Phenotype; Plant Roots; Psychiatrist; Psychologist; Psychopathology; Qualifying; Research Personnel; Resources; Role; Sample Size; Sampling; Siblings; Signal Transduction; Site; Substance Addiction; Susceptibility Gene; Technology; Testing; aged; anti social; cost; data sharing; early onset; follow-up; genetic association; genetic epidemiology; lymphoblastoid cell line; multidisciplinary; proband

DESCRIPTION (provided by applicant): This application continues a multisite collaboration, initiated under DA 012845, to address critical issues in the genetic epidemiology of adolescent onset antisocial drug dependence. Addressing these issues requires sample sizes greater than a single site can reasonably attain, as well as the multidisciplinary expertise of psychiatrists, psychologists, and behavioral and molecular geneticists, that is difficult to provide at a single site. This collaboration includes longitudinal assessment of previously studied probands and siblings, and adds community controls. It will yield a total of ~800 clinical probands, together with their siblings, to assess differing developmental trajectories and clinical courses, and the role of comorbidity, early onset, and familial loading. After allowing for desistance, we anticipate a final sample of ~600 persistent cases, together with their siblings, and a matched sample of ~600 control subjects, for genetic association analyses of persistent, adolescent onset, antisocial substance dependence. The current application will use dense SNP association mapping to identify genetic loci predisposing to this pattern of behavior. The specific aims of the project are as follows: 1) We will complete the five year follow-up assessment of ~800 clinical probands, aged 19 though 23 years at follow-up, and their siblings, and ascertain a sample of matched control subjects from our existing databases together with 300 newly ascertained control subjects. The new assessments will be conducted at the San Diego and Denver sites. 2) We will assess differing developmental trajectories and clinical courses, and the role of comorbidity, early onset, and familial loading on these. The data set we are collecting would, even in the absence of a single DMA sample, represent a unique, and unsurpassed, research resource for studying the development and familial influences on adolescent antisocial drug dependence. 3) We will use Affymetrix SNP chip technology to genotype an average of 25 SNPs in each of 200 candidate genes for drug dependence vulnerability and/or conduct disorder. 4) We will conduct association analyses using the -600 persistent cases and their ~600 matched controls, and then conduct confirmatory tests of the best signals using a within-family association analysis (Laird and Lange, 2006). These analyses will confirm the significance and robustness of genetic associations with adolescent onset persistent antisocial drug dependence. 5) Through a continuation of our NIDA Genetics Consortium data sharing agreement, we will share all the core substance dependence and psychopathology phenotypic data, and DNA from lymphoblastoid cell lines established for the multisite samples. Our Affymetrix SNP chip will be made available, at cost, to any qualified researcher.

描述（由申请人提供）：此申请继续根据DA 012845启动的多站点协作，以解决青少年发作反社会药物依赖性遗传流行病学中的关键问题。解决这些问题需要比单个站点更大的样本量，以及精神科医生，心理学家以及行为和分子遗传学家的多学科专业知识，这些专业知识很难在一个地点提供。这项合作包括对先前研究的证据和兄弟姐妹的纵向评估，并增加了社区控制。它将产生约800个临床证据，以及它们的兄弟姐妹，以评估不同的发展轨迹和临床课程，以及合并症，早期发作和家族负荷的作用。允许避免后，我们预计最终样本的持续情况以及其兄弟姐妹的最终样本以及约600个对照受试者的匹配样本，用于持续的，青少年发作，反社会药物依赖性的遗传关联分析。当前的应用程序将使用密集的SNP关联映射来识别这种行为模式的遗传基因座。该项目的具体目的如下：1）我们将完成五年的随访评估，对〜800个临床证据，享年19岁，但随访23岁及其兄弟姐妹，并确定来自现有数据库的匹配对照对象的样本，以及300个新确定的对照对象。新的评估将在圣地亚哥和丹佛站点进行。 2）我们将评估不同的发展轨迹和临床课程，以及合并症，早期发作和家族负荷在这些方面的作用。即使在没有单个DMA样本的情况下，我们收集的数据集也代表着一种独特且无与伦比的研究资源，用于研究对青少年反社会药物依赖性的发展和家庭影响。 3）我们将使用Affymetrix SNP芯片技术在200个候选基因中平均为25个SNP，以用于药物依赖性脆弱性和/或行为障碍。 4）我们将使用-600持续情况及其约600个匹配的对照进行关联分析，然后使用家庭内部关联分析对最佳信号进行确认测试（Laird and Lange，2006年）。这些分析将证实遗传关联与青少年持续性反社会药物依赖性的重要性和鲁棒性。 5）通过延续我们的NIDA遗传联盟数据共享协议，我们将共享所有核心物质依赖性和心理病理学表型数据，以及为多站点样品建立的淋巴母细胞细胞系的DNA。我们的Affymetrix SNP芯片将以成本为任何合格的研究人员提供。