MOLECULAR GENETICS OF SCHIZOPHRENIA

精神分裂症的分子遗传学

• 批准号: 6392701
• 负责人: William Byerley
• 金额: $ 11.59万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6392701
• 关键词: African American; Australia; European; blood chemistry; caucasian American; clinical research; data management; diagnosis design /evaluation; family genetics; gene frequency; gene interaction; genetic disorder; genetic markers; genome; genotype; human subject; interview; linkage mapping; mental disorder diagnosis; mental health epidemiology; molecular genetics; questionnaires; schizophrenia; siblings; tissue /cell culture

DESCRIPTION: (Adapted from investigator's abstract) Susceptibility to schizophrenia appears to be transmitted in part through a complex genetic mechanism involving interaction of multiple genes, each of relatively small effect. Detection of such loci through genetic linkage studies is likely to require a very large sample of multiply affected pedigrees. In response to RFA MH-99-005, nine investigators propose a Collaborative Study of Mental Disorders to collect in three years a sample of 517 affected sibling pairs (ASPs) with DSM-IV schizophrenia, to complete a genome scan of these pedigrees for multipoint ASP analysis to detect susceptibility loci, and to share biological materials, genotypes and blinded clinical data with the scientific community through an NIMH-sponsored mechanism. Each site will recruit families in a large geographic area, using an opportunistic ascertainment strategy and efficient assessment procedures to maximize the number of ASPs collected. Subjects suspected of having schizophrenia will be assessed with the Diagnostic Interview for Genetic Studies supplemented by information from the Family interview for Genetic studies and medical records. Diagnoses will be made by consensus best-estimate procedures. Interviewer training and quality assurance monitoring of protocol adherence will be provided for all sites. Blood specimens will be obtained from all individuals with psychotic disorders plus their parents and (when both parents are not available) up to two additional siblings to provide genetic phase information. Permanent cell lines will be created and DNA extracted at the NIMH-sponsored Center for Genetic Studies. All clinical data will be merged regularly into a central study database, and blinded data transmitted to the Center for Genetic Studies. At the end of the four-year project period, biological materials and blinded pedigree and clinical data will be made available to scientific community for genetic studies of schizophrenia and related disorders. In year 4, a genome scan will be undertaken at CIDR (if approved) or at the University of Chicago. Affected subjects and relatives needed for phase information will be genotyped using the latest screening map, currently the Weber Version 9 Linkage Mapping Set, containing 387 microsatellite markers at approximately 10 cM spacing. The primary statistical approach will be multipoint analysis of allele sharing in affected individuals, with DSM-IV schizophrenia defined as affected. Secondary analyses will also be carried out. Power analyses suggest that this study would have excellent power to detect loci associated with lambda sibs of 1.4, and moderate power for a value of 1.3, i.e., loci with relatively small etiologic effects.

描述：（改编自研究者摘要） 精神分裂症似乎部分通过复杂的遗传途径传播 涉及多个基因相互作用的机制，每个基因相对较小， 效果通过遗传连锁研究检测这些基因座很可能 需要非常大的多重影响的家系样本。关于RFA MH-99-005，九名研究人员提出了一项精神障碍的合作研究 在三年内收集了517个受影响的兄弟姐妹对（ASP）的样本， DSM-IV精神分裂症，以完成这些家系的基因组扫描， 多点ASP分析，以检测易感基因座，并共享生物学特性， 材料、基因型和盲态临床数据与科学界 通过NIMH赞助的机制。 每个站点将在一个大的地理区域内招募家庭，使用 机会主义查明战略和有效的评估程序， 最大化收集的ASP数量。疑似受试者 精神分裂症将通过遗传学诊断访谈进行评估。 研究补充了来自遗传学家庭访谈的信息 研究和医疗记录。诊断将通过共识最佳估计进行 程序.访谈者培训和方案质量保证监测 将为所有研究中心提供依从性。血液样本将从以下来源获得： 所有患有精神障碍的人加上他们的父母， 父母不可用）最多两个额外的兄弟姐妹，以提供遗传 相位信息将建立永久细胞系，并在 NIMH赞助的遗传研究中心。将合并所有临床数据 定期输入中央研究数据库，并将设盲数据传输至 遗传学研究中心。在四年项目期结束时， 将制作生物材料和盲态系谱和临床数据 科学界可用于精神分裂症的遗传研究， 相关疾病。 在第4年，将在CIDR（如果获得批准）或 芝加哥大学。阶段所需的受影响受试者和亲属 信息将使用最新的筛选图进行基因分型，目前， Weber第9版连锁图谱集，包含387个微卫星标记， 大约10厘米的间距。主要统计方法将是 用DSM-IV对受影响个体的等位基因共享进行多点分析 精神分裂症定义为受影响。还将进行次要分析。 功效分析表明，本研究具有极好的功效来检测 与λ同胞相关的基因座为1.4，并且值为1.3的中等功率， 也就是说，致病作用相对较小的位点。