Case Control Candidate Gene Study of Addiction

描述（由申请人提供）：虽然大多数人都使用过可能上瘾的物质，如尼古丁和酒精，但只有少数人会上瘾。来自家庭、双胞胎和收养研究的证据强烈表明，对多种物质的依赖存在共同的遗传倾向，最近的研究已经开始确定与成瘾相关的特定基因。该建议是一项极端表型的候选基因关联研究，使用NIDA资助的遗传流行病学项目“可卡因依赖的家庭研究”中收集的数据和遗传物质。本研究对可卡因依赖病例和非依赖社区对照进行了广泛的访谈，并收集了血液样本用于未来的遗传分析。病例是在化学依赖治疗环境中被确定为可卡因依赖的个体，93%的人表现出多种物质依赖。对照组由从未表现出对任何物质依赖的以社区为基础的受试者组成。候选基因将使用最先进的技术进行基因分型。本研究的目的是：目的1：在多物质依赖病例和非依赖对照中检查候选基因。1536个候选基因snp的基因分型将通过遗传疾病研究中心（CIDR）完成。目的2：随访与额外基因分型的显著关联，以进一步表征与多物质依赖的关联。此外，在项目的第2年和第3年，该研究将继续检查和测试其他研究人员发现的基因。以下目标本质上是探索性的，并将允许进一步产生假设-目标3：在确定显著关联后，检查种族，性别，共病和其他新表型与“高危”等位基因，基因型和单倍型的影响。目标4：利用基因-基因和基因-环境相互作用的额外遗传分析来检查物质依赖和定量表型的复杂遗传学。该项目采用多学科方法，汇集了许多领域的专业知识来研究成瘾的复杂问题。该提案的数据将成为NIDA遗传学联盟的一部分，供科学界使用。

DESCRIPTION (provided by applicant): Though most people have used potentially addicting substances such as nicotine and alcohol, only a minority of the population becomes addicted. Evidence from family, twin and adoption studies strongly suggests that there is a common genetic predisposition for dependence across multiple substances and recent studies have begun to identify specific genes associated with addiction. This proposal is a candidate gene association study of extreme phenotypes using data and genetic material collected in the NIDA funded genetic epidemiology project "A Family Study of Cocaine Dependence." This study conducted extensive interviews on cocaine dependent cases and non-dependent community based controls, and blood samples were collected for future genetic analysis. Cases are individuals who were identified in chemical dependency treatment settings with cocaine dependence and 93 percent exhibited poly-substance dependence. The control group consists community-based subjects who have never exhibited dependence on any substance. Candidate genes will be targeted for genotyping using state of the art technology. The aims of this study are: Aim 1: To examine candidate genes in polysubstance dependent cases and non-dependent controls. Genotyping of 1536 SNPs across candidate genes will be completed through the Center for Inherited Disease Research (CIDR). Aim 2: To follow up significant associations with additional genotyping to further characterize associations with polysubstance dependence. Additionally, in years 2 and 3 of the project, the study will pursue the examination and testing of genes identified by other investigators. The following aims are exploratory in nature and will allow further generation of hypotheses- Aim 3: To examine the influence of ethnicity, gender, comorbidity, and other novel phenotypes with the "at risk" alleles, genotypes, and haplotypes after significant associations are determined. Aim 4: To examine complex genetics of substance dependence and quantitative phenotypes using additional genetic analyses of gene-gene and gene-environment interaction This project uses a multidisciplinary approach, bringing together expertise in many domains to study the complex problem of addiction. Data from this proposal will be become part of the NIDA Genetics Consortium to be made available to the scientific community.