GENETIC LINKAGE STUDY OF SCHIZOPHRENIA

精神分裂症的遗传连锁研究

• 批准号: 2816022
• 负责人: MING T. TSUANG
• 金额: $ 85.88万
• 依托单位: MASSACHUSETTS MENTAL HEALTH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2816022
• 关键词: Chinese; clinical research; diagnosis quality /standard; family genetics; gene expression; genetic disorder; genetic susceptibility; genotype; human genetic material tag; human population genetics; human subject; human tissue; interview; linkage mapping; mental disorder diagnosis; schizophrenia; tissue resource /registry

It is proposed to study 90 sib-pairs with the disorder. Specific aims are: (1) to clinically assess a pedigree sample having adequate power to detect genes for schizophrenia; (2) to conduct a genome scan to find such loci; and (3) to transmit all data to the NIMH designated cell repository and data management centers. The goals will be attained by achieving the following: (1) from Taiwan and China, 900 Han Chinese sib- pairs having DSM-IV schizophrenia will be collected. (2) The investigators will examine all family members using the Diagnostic Interview for Genetic Studies and the Family Interview for Genetic Studies. The PI participated in the development and field testing of these interviews and has an already established training program for their use. They have been translated into Mandarin by the Taiwanese investigators, who have used them in prior studies. (3) Blood samples will be sent to the NIMH designated cell repository for creation of lymphoblastoid cell lines. (4) Clinical data will be entered using the database software created for the NIMH Human Genetics Initiative. Data will be vetted and sent to the NIMH designated data management center. (5) The investigators will complete a genome scan using 450 markers spaced at an average of 10 cM intervals using markers that have been optimized for use in the Han Chinese population. The scan will be completed with no cost to the NIMH through an agreement with Millenium Pharmaceuticals, a biotechnology company in the Boston area that the PI has worked with on a prior genetic linkage study of schizophrenia. All genetic analyses will be approved by the consultant, Eric Lander, Ph.D. (6) all clinical data will be made available to the scientific community by the end of the funding period. All genotypes will be available on year after they are created but no later than a year after the funding period. This project is feasible because: (1) The PI has already coordinated one multi-site genetic linkage study of schizophrenia and has participated in a second. (2) The investigators have a longstanding relationship with the Taiwanese collaborators and an effective, albeit, more recent working relationship with the Chinese collaborator. (3) The investigators have conservatively estimated that each site has access to more than enough available families having two schizophrenic siblings. (4) The PI's Harvard team has had prior experience collaborating on genotyping and linkage analysis projects with Millennium Pharmaceuticals. This, and Millennium's prior genotyping experience shows that the genotyping phase of the work is feasible.

建议对 90 对患有该疾病的同胞进行研究。 具体目标 是：（1）临床评估具有足够功效的谱系样本 检测精神分裂症基因； (2) 进行基因组扫描寻找 这样的基因座； (3) 将所有数据传输至 NIMH 指定单元 存储库和数据管理中心。这些目标将通过以下方式实现 实现以下目标：（1）来自台湾和中国大陆的 900 名汉族同胞 将收集患有 DSM-IV 精神分裂症的配对。 (2) 的 调查人员将使用诊断仪检查所有家庭成员 遗传学研究访谈和遗传学家庭访谈 研究。 PI参与了系统的开发和现场测试 这些访谈并已经制定了培训计划 他们的用途。 已经被台湾人翻译成普通话了 研究人员在之前的研究中使用过它们。 (3) 血液样本 将被发送到 NIMH 指定的细胞存储库以创建 淋巴母细胞系。 (4) 临床数据将使用 为 NIMH 人类遗传学计划创建的数据库软件。 数据 将被审查并发送至 NIMH 指定的数据管理中心。 (5) 研究人员将使用 450 个标记完成基因组扫描 使用已标记的标记，平均间隔 10 cm 针对汉族人群进行了优化。 扫描将是 通过与 Millenium 达成协议，NIMH 无需支付任何费用即可完成 Pharmaceuticals 是波士顿地区的一家生物技术公司，PI 之前曾参与过精神分裂症的遗传连锁研究。 全部 遗传分析将得到顾问 Eric Lander 博士的批准。 (6) 所有临床数据将向科学界公开 到资助期结束时。 所有基因型均可在 创建后一年但不迟于资助后一年 时期。 这个项目是可行的，因为： (1) PI 已经 协调一项精神分裂症的多位点遗传连锁研究 已参加第二次。 (2) 调查人员长期 与台湾合作者的关系以及有效的、尽管 最近与中国合作者的工作关系。 (3) 的 调查人员保守估计每个站点都可以访问 给足够多的有两名精神分裂症患者的家庭 兄弟姐妹。 (4) PI哈佛团队有过往经验 与以下机构合作开展基因分型和连锁分析项目 千禧制药。 这和千禧年之前的基因分型 经验表明，基因分型阶段的工作是可行的。