GENETIC LINKAGE STUDY OF SCHIZOPHRENIA

精神分裂症的遗传连锁研究

• 批准号: 6469979
• 负责人: MING T. TSUANG
• 金额: $ 2.86万
• 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/6469979
• 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.

建议研究90个同胞对的障碍。 具体目标 是：（1）临床评估具有足够功效的谱系样本 检测精神分裂症的基因;（2）进行基因组扫描， （3）将所有数据传输到NIMH指定的小区 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）从台湾和中国，900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工具检查所有家庭成员。 遗传学研究访谈和遗传学家庭访谈 问题研究主要研究者参与了 这些面试，并有一个已经建立的培训计划， 他们的使用。 他们已经被台湾人翻译成普通话 研究人员在之前的研究中使用过它们。(3)血样 将被发送到NIMH指定的细胞库， 淋巴母细胞样细胞系。(4)临床数据将使用 为NIMH人类遗传学倡议创建的数据库软件。 数据 将被审查并发送到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 以平均10 cM的间隔，使用已经被 优化用于中国汉族人群。 扫描将是 通过与Millenium的协议，NIMH无需支付任何费用即可完成 制药公司，波士顿地区的一家生物技术公司，PI 曾参与过精神分裂症的遗传连锁研究 所有 遗传分析将由顾问Eric Lander博士批准。 (6)所有的临床数据将提供给科学界 在融资期结束时。 所有基因型将在 一年后，他们被创建，但不迟于一年后，资金 期 该项目是可行的，因为：（1）PI已经 协调一项精神分裂症多位点遗传连锁研究， 参加了第二次。(2)调查人员长期以来 与台湾合作者的关系，以及一个有效的，尽管， 最近与中国合作伙伴建立了合作关系。(3)的 研究人员保守估计，每个站点都可以访问 有两个精神分裂症患者的家庭 兄妹(4)PI的哈佛团队有过 在基因分型和连锁分析项目上与 千禧制药 这个加上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。

项目成果

Association of older paternal age with earlier onset among co-affected schizophrenia sib-pairs.

在共同患病的精神分裂症同胞对中，父亲年龄较大与发病较早之间存在关联。

• DOI: 10.1017/s0033291715000203
• 发表时间: 2015
• 期刊: Psychological medicine
• 影响因子: 6.9
• 作者: Wang,SH;Liu,CM;Hwu,HG;Hsiao,CK;Chen,WJ
• 通讯作者: Chen,WJ

Further evidence for an association of G72/G30 with schizophrenia in Chinese.

G72/G30 与中国人精神分裂症相关的进一步证据。

• DOI: 10.1016/j.schres.2008.07.016
• 发表时间: 2009
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Shi,Jiajun;Badner,JudithA;Gershon,ElliotS;Chunyu,Liu;Willour,VirginiaL;Potash,JamesB
• 通讯作者: Potash,JamesB

Handedness and schizotypy in non-psychotic relatives of patients with schizophrenia.

• DOI: 10.1080/1357650x.2010.511646
• 发表时间: 2011-11
• 期刊: Laterality
• 影响因子: 1.4
• 作者: Tsuang HC;Liu CM;Hwang TJ;Hsieh MH;Faraone SV;Tsuang MT;Hwu HG;Chen WJ
• 通讯作者: Chen WJ

Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits.

• DOI: 10.1371/journal.pone.0150435
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Liu YL;Wang SC;Hwu HG;Fann CS;Yang UC;Yang WC;Hsu PC;Chang CC;Wen CC;Tsai-Wu JJ;Hwang TJ;Hsieh MH;Liu CC;Chien YL;Fang CP;Faraone SV;Tsuang MT;Chen WJ;Liu CM
• 通讯作者: Liu CM

The DAO gene is associated with schizophrenia and interacts with other genes in the Taiwan Han Chinese population.

DAO 基因与精神分裂症相关，并与台湾汉族人群中的其他基因相互作用。

• DOI: 10.1371/journal.pone.0060099
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Yang,Hsin-Chou;Liu,Chih-Min;Liu,Yu-Li;Chen,Chia-Wei;Chang,ChienChing;Fann,CathySJ;Chiou,Jen-Jie;Yang,Ueng-Cheng;Chen,Chun-Houh;Faraone,StephenV;Tsuang,MingT;Hwu,Hai-Gwo
• 通讯作者: Hwu,Hai-Gwo