GENOME-WIDE ANALYSIS FOR ADDICTION SUSCEPTIBILITY GENES

描述(改编自申请人摘要)：这是一份R01申请 为确定与药物依赖有关的染色体标记提供资金。对.的使用 非法、高度上瘾的毒品是#年的一个重大公共卫生和法律问题。 美国和世界各地。迫切需要新的 药物治疗方案。因为有很大一部分人 对滥用药物的易感性有遗传基础，决定了潜在的 遗传因素将有助于确定治疗干预的新靶点。一 识别复杂性状中的遗传因素的方法是使用 非参数连锁分析，如影响同胞对方法。然而， 要确定大量符合的同胞对是非常困难的 药物滥用/依赖，特别是在积极滥用药物的对象中 毒品。调查人员将通过确定一个相对的 一组稳定的阿片依赖受试者及其受影响的兄弟姐妹 大量的美沙酮维护客户。阿片成瘾者登记参加 美沙酮计划可能是严重上瘾的最稳定的群体 可用于临床研究的个人，因为他们几乎来到临床 每天去拿美沙酮，去见心理咨询师，社会工作者， 精神病学家和医生经常这样做。从20,000个客户池中， 他们将确定450对兄弟姐妹，他们都在接受美沙酮治疗 程序。这些受试者将接受SCID和各种心理学的评估 确定精神状况、个性和气质的措施 与物质依赖相关的特征。两个阶段的全基因组搜索 因为与阿片类药物依赖有关的遗传位点将发生；第一个发生在10% 厘摩根分辨率。阳性标记物将在第二阶段进行追踪， 1-3厘米测量。到项目结束时，这将与 人类基因组计划完成后，他们将能够分析所有 映射到连锁标记的特定候选基因。

DESCRIPTION (adapted from applicant's abstract): This is an R01 application for funding to identify chromosomal markers linked to drug dependence. The use of illicit, highly addictive drugs is a major public health and legal problem in the United States and around the world. There is an urgent need for new pharmacological treatment options. Since a substantial fraction of the vulnerability to abuse drugs has a genetic basis, determining underlying genetic factors will help identify new targets to therapeutic intervention. One approach used to identify genetic factors in complex traits is to use non-parametric linkage analysis, such as the affected sib pair method. However, it is very difficult to ascertain large numbers of sib pairs concordant for drug abuse/dependence, especially in subjects who are actively abusing hard drugs. The investigators will address this problem by ascertaining a relatively stable group of opiate dependent subjects and their affected siblings in a very large population of methadone maintenance clients. Opiate addicts enrolled in methadone programs are perhaps the most stable group of heavily addicted individuals available for clinical study, since they come to clinic almost every day to pick up methadone, and meet with counselors, social workers, psychiatrists and medical doctors frequently. From a pool of 20,000 clients, they will identify 450 sib pairs who are both being treated in a methadone program. These subjects will be assessed by SCID and various psychological measures to identify psychiatric conditions and personality and temperament traits associated with substance dependence. A two stage, genome-wide search for genetic loci linked to opiate dependence will take place; the first at a 10 centimorgan resolution. Positive markers will be followed up in a second stage, 1-3 centimorgan survey. By the end of the project, which will coincide with the completion of the human genome project, they will be able to analyze all of the specific candidate genes that map to linked markers.