Genetics of Opioid Dependence in a Hmong (Thai) Isolate

描述（由申请人提供）：阿片类药物依赖（OD）是一种常见的疾病，导致相当大的社会，医疗和精神残疾，在美国和国际上。目前的数据表明遗传因素在其病因学中的重要性，并且存在遗传异质性和复杂遗传的强烈预期。到目前为止，还没有人类研究明确确定了导致OD的基因的位置。然而，复杂性状的遗传分析方法的进展，以及最近在鉴定专业（例如，孤立的）人群，使这成为启动此类研究的最佳时间。我们的小组前往泰国北方的“金三角”（罂粟在当地生长，阿片类药物依赖率很高的地区），以研究几个民族之一的OD遗传学（即，Hmong）hill tribes.我们已经确定了一个理想的地理和文化上孤立的村庄，大约有2,500名居民（1750名苗族人，来自4个主要家庭/氏族），其中大约200名村民据报道有OD的终身病史（即，估计终生流行率2.10%）。存在明显的历史瓶颈、文化上禁止与部落外通婚、庞大而完整的谱系以及相对缺乏其他滥用药物，这些都可能导致更大的遗传和/或环境同质性。在当前修订的应用程序中，我们建议建立一个全面的，社区范围内的收集所有合格的受试者从扩展苗族谱系广泛的特点是阿片类药物（和其他物质）依赖使用SSADDA（药物依赖和酒精中毒的半结构化评估）的可行性具体而言，共200苗族村民将在2-vear期间进行研究。将通过访谈建立谱系关系，并通过遗传学方法进行确认。我们相信，这些研究为确定OD的易感位点提供了重要的，也许是独特的强大优势。

DESCRIPTION (provided by applicant): Opioid dependence (OD) is a common disorder resulting in considerable social, medical and psychiatric disability, both in the U.S. and internationally. Current data demonstrate the importance of genetic factors in its etiology, and there is a strong expectation of genetic heterogeneity and complex inheritance. To date, no human research has unequivocally established locations of genes contributing to OD. However, advances in methods for the genetic analysis of complex traits, and recent successes in identifying genes for common diseases in specialized (e.g., isolated) populations, make this an optimal time to initiate such a study. Our group has traveled to the "Golden Triangle" of Northern Thailand (a region where the opium poppy grows indigenously and where rates of opioid dependence are high) in order to study the genetics of OD in one of several ethnic (i.e., Hmong) hill tribes. We have identified what appears to be an ideal geographically and culturally isolated village of approximately 2,500 inhabitants (1750 Hmong descended from 4 primary families/clans) of whom roughly 200 villagers are reported to have a lifetime history of OD (i.e., estimated lifetime prevalence rates 2.10%). The presence of apparent historical bottlenecks, cultural prohibitions against marrying outside the tribe, large and intact pedigrees, and relative absence of other drugs of abuse are likely to contribute to greater genetic and/or environmental homogeneity. In the current revised application, we propose to establish the feasibility of conducting a comprehensive, community-wide collection of all eligible subjects from extended Hmong pedigrees extensively characterized for opioid (and other substance) dependence using the SSADDA (Semi-Structured Assessment of Drug Dependence and Alcoholism) Specifically, a total of 200 Hmong villagers will be studied over a 2-vear period. Pedigree relationships will be established by interview and confirmed by genetic methods. Such studies, we believe, afford significant, perhaps uniquely powerful, advantages for identifying susceptibility loci for OD.