Genetics of Schizophrenia in Oceanic Palau.

我们的主要目标是确定导致精神分裂症和其他疾病的基因变异。 帕劳海洋人口中的精神障碍(以下称为SCZ)。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项 调查人员与帕劳政府之间的长期关系。我们有家谱 关于数千个人的信息，他们代表着从大洋航空公司完全确定 在帕劳的人口中，这是一个令人信服的资源，用于链接和关联绘图。我们建议 通过对250,000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(SNPs)，使用Affymetrix芯片技术。我们用这些基因型别 寻找符合传统假设的变异--SCZ的风险由遗传决定 受影响的个体携带的变异。我们还将使用这些数据来检验一个新的假设--即最初的 SCZ的易感性是在胎儿发育过程中由一个或多个环境应激源产生的，但它是 由母体遗传易感性促成的应激，使胎盘！环境不能 充分缓冲发育中的胎儿。有效地搜索影响这两个级别的风险的变量 (母亲或个人)，我们建议基本上对所有250名受SCZ影响的个人，150名母亲进行基因分型。 被诊断为SCZ的个体，以及100名对照组。另外450个人的DMA将被使用 用于后续分析。将为这一人群收集一组丰富的孕产妇风险因素，并将其用于我们的 分析。统计分析将以识别共享更多的扩展单倍型为目标 经常是偶然的(无论是在受影响的个人还是他们的母亲身上)。该等物品的识别 单倍型将由该海洋和其他海洋的延伸连锁不平衡特征所促进 人口。分子和精细图谱研究将确定风险基因座。我们相信这项研究是独一无二的 SCZ遗传学研究的群体、样本、研究团队及其假设和新颖性 接近。

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.