1/2 Expanding Rapid Ascertainment Networks Of Schizophrenia Families In Taiwan

1/2 扩大台湾精神分裂症家族快速查明网络

• 批准号: 7920227
• 负责人: MING T. TSUANG
• 金额: $ 116.86万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920227
• 关键词: Accounting; Affect; Age; Biocompatible Materials; Biological; Candidate Disease Gene; Chinese People; Clinical; Clinical Data; Collection; Complex; Conflict (Psychology); Copy Number Polymorphism; Data; Development; Disease; Early treatment; Etiology; Failure; Family; Family member; Funding; Genes; Genetic; Genetic Epistasis; Genomics; Genotype; Goals; Haplotypes; Heritability; Human Genetics; Meta-Analysis; Methods; Molecular; National Institute of Mental Health; Nuclear Family; Phenotype; Play; Prevention Protocols; Protocols documentation; Request for Applications; Research Infrastructure; Research Methodology; Research Personnel; Resources; Risk; Role; Sampling; Schizophrenia; Screening procedure; Series; Single Nucleotide Polymorphism; Site; Staging; Subgroup; Surveys; Susceptibility Gene; Symptoms; Taiwan; Testing; Twin Studies; Variant; Work; base; case control; clinical infrastructure; cost; design; disorder risk; gene environment interaction; gene interaction; genetic linkage; genetic linkage analysis; genome wide association study; genome-wide; genome-wide linkage; insight; meetings; novel; novel therapeutics; proband; repository; season of birth

DESCRIPTION (provided by applicant): This proposal responds to Request for Applications RFA-MH-08-131, which seeks Collaborative R01 applications that propose to enrich pre-existing resources for schizophrenia in the NIMH Human Genetics Initiative and to apply genomic methods to further our understanding of the molecular etiology of the disorder. The overarching aims of this proposal are to quickly and cost-effectively ascertain a large sample of trio families affected by schizophrenia, and to discover causal variants for the disorder in the first family-based genome-wide association study (GWAS) of the illness. In our recently completed NIMH-funded Genetic Linkage Study of Schizophrenia (R01MH059624; PI: Ming T. Tsuang), we established a large and efficient ascertainment network and infrastructure in Taiwan, which will again be utilized and expanded in the proposed study. Through additional ascertainment within this framework, we will collect an aggregate sample of 5,000 trios with adequate power for detecting in a GWAS those variants that make even small contributions to the risk for the disorder. We will meet the overarching goals of this project by accomplishing several Specific Aims, as follows: 1) Supplement our previously collected sample of 1,200 Han Chinese schizophrenia-affected nuclear families from Taiwan by rapidly screening and collecting an additional 3,800 trios from ten ascertainment sites in Taiwan; 2) Assess the association of schizophrenia with a genome-wide panel of single-nucleotide polymorphisms and their constituent haplotypes; 3) Perform a genome-wide survey for copy-number variations related to schizophrenia; 4) Test for gene-gene interactions (epistasis); 5) Test for gene-environment interactions, such as the well-established effect of season of birth; 6) Analyze quantitative schizophrenia phenotypes, such as symptom scores and age at onset; and 7) Enhance the NIMH Genetics Initiative collections by sending all clinical data, biomaterials, and genotypes to the appropriate repositories. The project would achieve the goals of the RFA by enriching the existing resources of the NIMH Human Genetics Initiative and by applying the latest genomic research methods to further our understanding of the molecular etiology of the disorder. Also, by capitalizing on an existing clinical infrastructure and an efficient screening and assessment protocol, we will obtain a well-powered sample in a very rapid and cost-effective manner.

描述（由申请人提供）：该提案响应申请的请求RFA-MH-08-131，该申请寻求协作R01应用程序，建议在NIMH人类遗传学的创始人中获得精神分裂症的先前资源，并采用基因组方法，以进一步采用我们对疾病的分子病因的理解。该提案的总体目的是快速，成本效率地确定大量受精神分裂症影响的三重奏家族，并在第一个基于家庭的基因组范围内的疾病研究（GWAS）中发现该疾病的因果变异。在我们最近完成的NIMH资助的精神分裂症遗传联系研究（R01MH059624; PI：Ming T. Tsuang）中，我们在台湾建立了一个庞大而有效的确定网络和基础设施，该网络将在提议的研究中再次利用和扩展。通过此框架中的其他确定，我们将收集5,000个三重奏的总样本，并具有足够的功率，以便在GWAS中检测到那些对疾病风险贡献的变体。我们将通过实现多个具体目标来实现该项目的总体目标，如下所示：1）补充了我们先前收集的从台湾的1,200汉中国精神分裂症影响的核心家族的样本，并通过迅速筛选并从台湾十个确定地点收集3,800个三人组。 2）评估精神分裂症与全基因组的单核苷酸多态性及其成分单倍型的关联； 3）对与精神分裂症相关的拷贝数变异进行全基因组调查； 4）基因 - 基因相互作用的测试（epitisasis）； 5）测试基因环境相互作用，例如出生季节的良好影响； 6）分析定量精神分裂症表型，例如症状评分和发作年龄； 7）通过向适当的存储库发送所有临床数据，生物材料和基因型来增强NIMH遗传学计划的收集。该项目将通过丰富NIMH人类遗传学计划的现有资源，并应用最新的基因组研究方法来进一步了解我们对疾病分子病因的理解，从而实现RFA的目标。同样，通过利用现有的临床基础设施和有效的筛查和评估方案，我们将以非常快速且具有成本效益的方式获得一个能力的样本。