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，无论是在美国还是在国际上。目前的数据表明，遗传因素在其病因中的重要性，并有强烈的期望遗传异质性和复杂的遗传。迄今为止，还没有一项人类研究明确确定了导致OD的基因位置。然而，复杂性状遗传分析方法的进步，以及最近在特定（例如，孤立）种群中鉴定常见疾病基因方面的成功，使现在成为开展此类研究的最佳时机。我们小组前往泰国北部的“金三角”（一个当地种植罂粟的地区，阿片类药物依赖率很高），以研究几个少数民族（即苗族）山地部落之一的OD遗传学。我们已经确定了一个理想的地理和文化孤立的村庄，大约有2500名居民（1750名苗族人来自4个主要家庭/氏族），其中大约200名村民据报道有终生吸毒史（即，估计终生患病率为2.10%）。存在明显的历史瓶颈、禁止与部落外的人通婚的文化禁忌、庞大而完整的血统以及相对缺乏其他滥用药物可能会导致更大的遗传和/或环境同质性。在当前修订的申请中，我们建议采用SSADDA（药物依赖和酒精中毒半结构化评估），对具有阿片类药物（和其他物质）依赖特征的扩展苗族血统的所有符合条件的受试者进行全面的、社区范围的收集，具体而言，将在2年的时间内对200名苗族村民进行研究。家谱关系将通过面谈建立，并通过遗传方法确认。我们相信，这样的研究为确定OD的易感性位点提供了重要的，也许是独特有力的优势。

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.