Admixture Mapping Schizophrenia Genes in Oceanic Palau

太平洋帕劳精神分裂症基因混合图谱分析

• 批准号: 6900314
• 负责人: BERNIE DEVLIN
• 金额: $ 13.46万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6900314
• 关键词: Pacific Islander; behavioral /social science research tag; behavioral genetics; family genetics; genetic susceptibility; human data; human genetic material tag; linkage disequilibriums; linkage mapping; statistics /biometry

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 approximately I 00BP due to disease introduced by European/American contact; the population has throughout its history experienced smaller effective population size than most modem 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).

描述（申请人摘要）：精神分裂症是一种毁灭性的精神疾病 导致难以言喻的痛苦和损失的综合症。尽管文化不同 和世界各地的环境、普遍性和表现形式 全世界的精神分裂症都是相似的。它的介绍和课程都没有 帕劳偏远海洋人口有所不同，但人口 帕劳的结构为探索遗传提供了独特的机会 这种毁灭性疾病的病因学。特别是帕劳的人口 起源较近，成立于距今约 2000 年前 (BP)；帕劳有 经历了至少两个重大瓶颈，在成立时和大约我 00BP 由于欧洲/美洲接触引入的疾病；人口有 纵观其历史，其有效人口规模比大多数国家都小 现代社会；帕劳显然经历了广泛的男性偏见 基因流。所有这些元素结合起来产生连锁不平衡 （LD）存在于常染色体和 X 染色体上的等位基因中，即使在 染色体上有很大的距离。 我们的主要目标是确定导致疾病发生的基因 利用帕劳的特色来治疗精神分裂症。除了其独特的 群体遗传学，帕劳精神分裂症发病率略高，2.77 男性为 1.24%，女性为 1.24%，而女性为 0.5% 至 1% 全球性别平均比率。岛上有156个？精神分裂症患者，其中 154 人贡献了 DNA。此外，我们还对 495 名重要亲属进行了抽样调查。因此 该项目不需要招聘。相反，我们可以专注于联动 LD 分析来绘制责任基因图谱。对于前者，扩展的血统和 联动工具可用；只需进行额外的基因分型和分析 必需的。对于后者，我们提出基于连锁的LD分析 结果和全基因组扫描，使用粗略的标记网格。我们的 初步结果证实了这两种方法可能取得成功。统计 将开发方法来补充 LD 的分子分析 本研究的组成部分。 该申请作为两个地点的协作 ROl 提交， 临床研究或精神障碍的机制。合作网站有 匹兹堡大学 (Devlin)、卡内基梅隆大学 (Roeder) 分包给皮特）和加州大学欧文分校（拜尔利）。