Genetics of Schizophrenia in Oceanic Palau.

太平洋帕劳精神分裂症的遗传学。

• 批准号: 7871106
• 负责人: MARINA MYLES-WORSLEY
• 金额: $ 10.89万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7871106
• 关键词: Accounting; Affect; Brain; Buffers; Characteristics; Chromosomes, Human, Pair 5; Complex; Data; Diagnosis; Diagnostic; Disease; Environment; Environmental Risk Factor; Family; Fetal Development; Fetus; Gene Frequency; Generations; Genes; Genetic; Genetic Models; Genetic Predisposition to Disease; Genetic Variation; Genome; Genome Scan; Genotype; Goals; Government; Haplotypes; Individual; Inheritance Patterns; Link; Linkage Disequilibrium; Literature; Location; Lod Score; Maps; Methods; Modeling; Molecular; Mothers; Nuclear Family; Palau; Parents; Pattern; Placenta; Population; Psychotic Disorders; Reporting; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Schizophrenia; Single Nucleotide Polymorphism; Statistical Methods; Stress; Technology; Testing; Update; Variant; density; environmental stressor; falls; fetal; follow-up; gene environment interaction; genetic analysis; genetic linkage analysis; genetic pedigree; genome wide association study; novel; offspring; programs; segregation; statistics

Our principal objective is to identify genetic variation that underlies liability to schizophrenia and other psychotic disorders (henceforth called Scz) in the Oceanic population of Palau. We will accomplish this goal by capitalizing on a wide range of scientific expertise and an incredible population sample obtained from a long-standing relationship between the investigators and the Government of Palau. We have genealogical information on many thousand individuals, who represent complete ascertainment from the Oceanic population of Palau, and constitute a compelling resource for linkage and association mapping. We propose a genome-wide study of linkage and association for risk to Scz by genotyping 500 individuals for 250,000 Single Nucleotide Polymorphisms (SNPs), using the Affymetrix chip technology. We use these genotypes to search for variation conforming to the conventional hypothesis - that risk to Scz is determined bygenetic variation carried by affected individuals. We will also usethese data to test a novel hypothesis - that initial liability to Scz is generated during fetal development by one or more environmental stressors, but it is facilitated by maternal genetic vulnerability to the stress, so that the placenta! environment cannot adequately buffer the developing fetus. To effectively search for variation affecting risk at either level (maternal or individual), we propose to genotype essentially all 250 individuals affected by Scz, 150 mothers of individuals diagnosed with Scz, and 100 control individuals. DMAfrom another 450 individual will be used for follow-up analyses. A rich set of maternal risk factors will be collected for this population and used in our analyses. Statistical analyses will target identification of extended haplotypes that are shared much more frequently than expected by chance (either in affected individuals or their mothers.) Identification of such haplotypes will be facilitated by extended linkage disequilibrium characteristic of this and other Oceanic populations. Molecular and fine-mapping studies will identify risk loci. We believe this study is unique among studies of Scz genetics for its population, sample, research team and the novelty of hypotheses and approach.

我们的主要目标是确定精神分裂症和其他疾病易感性的遗传变异。 精神障碍（以下称为SCZ）在帕劳的海洋人口。我们将实现这一目标 通过利用广泛的科学专业知识和从一个令人难以置信的人口样本， 调查人员与帕劳政府之间的长期关系。我们有家谱 关于数千人的信息，他们代表了海洋的完整确定 人口的帕劳，并构成了一个引人注目的资源的联系和关联绘图。我们提出 通过对25万人中的500人进行基因分型，对Scz风险的连锁和关联进行全基因组研究。 单核苷酸多态性（SNPs），使用Affyssin芯片技术。我们用这些基因型 寻找符合传统假设的变异-Scz的风险由遗传决定 受影响的个体所携带的变异。我们还将使用这些数据来测试一个新的假设-最初的 对Scz的易感性是在胎儿发育期间由一种或多种环境应激源产生的，但它是 促进了母体遗传易感性的压力，使胎盘！环境无法 充分缓冲发育中的胎儿。有效搜索影响任一水平风险的变异 （母亲或个人），我们建议基因型基本上所有250个个体受SCZ，150母亲， 被诊断患有Scz的个体和100名对照个体。将使用另外450人的DMA 进行后续分析。将收集这一人群的一组丰富的孕产妇风险因素，并用于我们的 分析。统计分析的目标将是识别扩展的单倍型， 经常比预期的机会（无论是在受影响的个人或他们的母亲。查明这类 单倍型将有助于扩展连锁不平衡特征，这和其他海洋 人口。分子和精细定位研究将确定风险位点。我们相信这项研究是独一无二的， SCZ遗传学研究的人口，样本，研究团队和假设的新奇， approach.

项目成果

Characterization of a Novel Mutation in SLC1A1 Associated with Schizophrenia.

• DOI: 10.1159/000433599
• 发表时间: 2015-10
• 期刊: Molecular neuropsychiatry
• 作者: Afshari P;Myles-Worsley M;Cohen OS;Tiobech J;Faraone SV;Byerley W;Middleton FA
• 通讯作者: Middleton FA

Familial transmission of schizophrenia in Palau: A 20-year genetic epidemiological study in three generations.

帕劳精神分裂症的家族传播：一项为期 20 年的三代遗传流行病学研究。

• DOI: 10.1002/ajmg.b.31171
• 发表时间: 2011
• 期刊: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
• 作者: Myles-Worsley,Marina;Tiobech,Josepha;Blailes,Francisca;Middleton,FrankA;Vinogradov,Sophia;Byerley,William;Faraone,StephenV
• 通讯作者: Faraone,StephenV