MOLECULAR GENETICS OF SCHIZOPHRENIA

描述：(改编自调查员摘要)易感性 精神分裂症似乎部分通过一种复杂的基因传播。 涉及多个基因相互作用的机制，每个基因都相对较小 效果。通过遗传连锁研究检测这些基因座可能会 需要一个非常大的多发病家系样本。对RFA的回应 MH-99-005，九名研究人员提出了一项关于精神障碍的合作研究 在三年内收集517对受影响的兄弟姐妹对(ASP)的样本 DSM-IV精神分裂症，完成这些家系的基因组扫描 多点ASP分析检测易感基因座，共享生物学信息 材料、基因分型和与科学界的盲目临床数据 通过NIMH赞助的机制。 每个网站都将在一个大的地理区域内招募家庭，使用 机会主义的查明战略和高效的评估程序 最大限度地增加收集的ASP数量。受试者涉嫌患有 精神分裂症将通过遗传学诊断访谈进行评估 由Genetic的家庭访谈提供的信息补充的研究 研究和医疗记录。诊断将通过一致的最佳估计做出 程序。面试官培训和礼仪质量保证监测 将为所有站点提供遵守规定。血液样本将从以下地点获得 所有患有精神障碍的人加上他们的父母和(如果两者都有 父母不可用)最多两个额外的兄弟姐妹提供基因 阶段信息。将创建永久细胞系并提取DNA NIMH赞助的遗传研究中心。所有临床数据将被合并 定期输入中央研究数据库，并将盲化数据传输到 遗传学研究中心。在四年项目期结束时， 将制作生物材料、盲家系和临床数据 可供科学界用于精神分裂症和 相关的障碍。 在第4年，将在CIDR(如果获得批准)或在 芝加哥大学。阶段所需的受灾对象和亲属 信息将使用最新的筛查地图进行基因分型，目前是 韦伯版本9连锁图谱集，包含387个微卫星标记，位于 间距约为10厘米。主要的统计方法将是 用DSM-IV多点分析受影响个体的等位基因共享 精神分裂症被定义为受影响的。还将进行二次分析。 能量分析表明，这项研究将具有极强的检测能力 与lambda同胞相关联的基因座为1.4，并且中等幂的值为1.3， 即病因学影响相对较小的基因座。

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.