GENOME-WIDE ANALYSIS FOR ADDICTION SUSCEPTIBILITY GENES

描述（改编自申请人摘要）：这是一个R 01申请， 资助确定与药物依赖有关的染色体标记。使用 非法、高度成瘾性药物是一个主要的公共卫生和法律的问题， 美国和世界各地。迫切需要新的 药物治疗选择。因为大部分的 药物滥用的脆弱性具有遗传基础，决定着 遗传因素将有助于确定治疗干预的新靶点。一 用于识别复杂性状中遗传因素的方法是使用 非参数连锁分析，如受影响的同胞对方法。然而，在这方面， 很难确定大量的同胞对是一致的， 药物滥用/依赖，尤其是在严重滥用药物的受试者中 毒品调查人员将通过确定一个相对 一组稳定的阿片类药物依赖受试者及其受影响的兄弟姐妹， 大量美沙酮维持治疗患者。阿片类药物成瘾者 美沙酮项目可能是最稳定的一组重度成瘾者， 可用于临床研究的个体，因为他们几乎 每天都去买美沙酮，去见辅导员，社工， 精神科医生和医生经常。从两万个客户中， 他们将确定450对兄弟姐妹， 程序.这些受试者将接受SCID和各种心理评估。 确定精神状况以及个性和气质的措施 与物质依赖有关的特征。两阶段全基因组搜索 与阿片类药物依赖相关的基因位点的第一个位点将在10 厘摩分辨率。阳性标志物将在第二阶段进行随访， 1-3厘摩根调查公司。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的 与连锁标记对应的特定候选基因。

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.