Admixture Mapping Schizophrenia Genes in Oceanic Palau

描述（申请人？精神分裂症是一种毁灭性的精神疾病， 导致无尽痛苦和损失的综合症。尽管文化不同 和环境的影响， 世界范围内的精神分裂症都是相似的。它的介绍和课程是没有 在帕劳的偏远海洋人口中不同，但人口 帕劳的结构提供了独特的机会，探索遗传 这种毁灭性疾病的病因。特别是，帕劳的人口 最近的起源，建立约2000年前（BP）;帕劳有 至少经历了两个重大瓶颈，在成立和最近由于 由欧洲/美洲接触引入的疾病（约200 BP）; 在整个历史上，人口的有效人口较少 比大多数现代社会都大;帕劳显然经历了广泛的 偏向男性的基因流所有这些元素联合收割机产生联动 常染色体和X染色体上等位基因之间的不平衡（LD）， 甚至在染色体上的相当远的距离也能检测到。 我们的主要目标是确定基因的基础责任， 利用帕劳的特点治疗精神分裂症。除了得天独厚的 人口遗传学，帕劳有轻微的精神分裂症，2.77 男性为1.24%，女性为0.5%至1%， 全世界的性别平均比率。有156？在岛上吗精神分裂症患者，其中 154人提供DNA此外，我们还抽样调查了495名关键亲属。因此 该项目无需招聘。相反，我们可以把重点放在 和LD分析来定位易感基因。对于前者，扩展谱系和 连锁工具是可用的;只有额外的基因分型和分析， 必需的.对于后者，我们提出了基于联系的LD分析 结果和全基因组扫描，它使用一个粗略的网格标记。我们 初步结果证实，这两种办法都可能取得成功。统计 将开发方法来补充LD的分子分析 这项研究的组成部分。 此应用程序是作为两个站点的协作ROI在 临床研究或精神疾病的机制。合作网站包括 匹兹堡大学（德夫林），卡内基梅隆大学（罗德， 皮特）和加州尔湾大学（拜尔利）。

DESCRIPTION (Applicant?s Abstract): Schizophrenia is a devastating psychiatric syndrome that causes untold suffering and losses. Despite differing cultures and environments around the world, the prevalence and presentation of schizophrenia worldwide is similar. Its presentation and course are no different in the Remote Oceanic population of Palau, but the population structure of Palau presents unique opportunities to explore the genetic etiology of this devastating illness. In particular, the population of Palau is of recent origin, founded about 2000 years before present (BP); Palau has undergone at least two substantial bottlenecks, at founding and recently due to disease introduced by European/American contact (approximately 200BP); the population has throughout its history experienced smaller effective population size than most modern societies; and Palau has apparently experienced extensive male-biased gene flow. All of these elements combine to generate linkage disequilibrium (LD) among alleles on autosomal and X chromosomes, which is detectable even at substantial distances on chromosomes. Our principal objective is to identify genes that underlie liability to schizophrenia by using the special features of Palau. In addition to its unique population genetics, Palau has a slightly elevated rate of schizophrenia, 2.77 percent in males and 1.24 percent in females, compared to the 0.5 to 1 percent sex-averaged rate worldwide. There are 156 ?on-island? schizophrenics, of whom 154 have contributed DNA. In addition, we have sampled 495 key relatives. Thus no recruitment is required for this project. Instead, we can focus on linkage and LD analyses to map liability genes. For the former, extended pedigrees and linkage tools are available; only additional genotyping and analyses are required. For the latter, we propose LD analyses on the basis of linkage results and a whole genome scan, which uses a coarse grid of markers. Our preliminary results confirm the likely success of both approaches. Statistical methods will be developed to complement the molecular analyses for the LD component of this study. This application is submitted as a two-site, collaborative ROl under the mechanism of the Clinical Studies or Mental Disorders. Collaborating sites are the University of Pittsburgh (Devlin), Carnegie Mellon University (Roeder, subcontract to Pitt) and University of California Irvine (Byerley).