THE GENETIC DETERMINANTS OF BIPOLAR DISORDER AND SCHIZOPHRENIA

双相情感障碍和精神分裂症的遗传决定因素

• 批准号: 7956255
• 负责人: TIFFANY A GREENWOOD
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956255
• 关键词: Biomedical Research; Bipolar Disorder; Candidate Disease Gene; Clinical; Cloning; Complex; Computer Retrieval of Information on Scientific Projects Database; Custom; Data; Disease; Dissection; Funding; Gene Chips; Genes; Genetic; Genetic Determinism; Genetic Heterogeneity; Genome; Genomics; Genotype; Grant; High Performance Computing; Information Networks; Institution; Methods; National Institute of Mental Health; Nature; Phenotype; Research; Research Personnel; Resources; Scanning; Schizophrenia; Signal Transduction; Source; Susceptibility Gene; United States National Institutes of Health; endophenotype; gene discovery; gene interaction; genetic association; genome wide association study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The discovery of genes predisposing to complex diseases, such as bipolar disorder and schizophrenia, has proven to be very difficult. Over the years, genome linkage scans have identified a number of regions that may harbor candidate genes, yet none of these linkage findings has led to cloning of causative genes for either disorder. This may be due to the modest nature of the linkage signals and the broad genetic regions they encompass, a likely result of the well-known clinical and genetic heterogeneity associated with bipolar disorder, schizophrenia, and psychiatric illness in general. Researchers have now turned to alternative strategies, such as the use of endophenotypes, candidate gene studies, and large-scale genomic association studies, in the hope that these methods may aid in the genetic dissection of complex disorders. We have undertaken several such projects to discover the underlying determinants of bipolar disorder and schizophrenia. In particular, as part of the Consortium on the Genetics of Schizophrenia (COGS) we have collected 12 endophenotypes for schizophrenia and are pursuing linkage studies, as well as a large scale candidate gene study through the use of a custom gene chip that has just complete genotyping. We will also pursue gene-gene interaction studies guided by the results of our genetic network analyses. Additionally, as part of the NIMH Genetics Initiative for Bipolar Disorder, which is participating in the genotyping initiative sponsored by the Genetic Association Information Network (GAIN), we will pursue whole genome association studies of bipolar disorder and related phenotypes. We anticipate that we will receive the genetic data for this project in October. As these are rather large-scale efforts, the computing requirements will be substantial, exceeding our current capabilities as far as efficiency is concerned.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 事实证明，发现诱发双相情感障碍和精神分裂症等复杂疾病的基因非常困难。多年来，基因组连锁扫描已经识别出许多可能含有候选基因的区域，但这些连锁发现都没有导致任何一种疾病的致病基因的克隆。这可能是由于连锁信号的适度性质及其所包含的广泛遗传区域，这可能是与双相情感障碍、精神分裂症和一般精神疾病相关的众所周知的临床和遗传异质性的结果。研究人员现在转向替代策略，例如使用内表型、候选基因研究和大规模基因组关联研究，希望这些方法可以帮助复杂疾病的遗传解析。我们已经开展了几个这样的项目，以发现双相情感障碍和精神分裂症的潜在决定因素。特别是，作为精神分裂症遗传学联盟 (COGS) 的一部分，我们收集了 12 种精神分裂症的内表型，并正在进行连锁研究，以及通过使用刚刚完成基因分型的定制基因芯片进行大规模候选基因研究。我们还将在遗传网络分析结果的指导下进行基因与基因相互作用的研究。此外，作为 NIMH 双相情感障碍遗传学计划的一部分，该计划正在参与由遗传关联信息网络 (GAIN) 赞助的基因分型计划，我们将开展双相情感障碍和相关表型的全基因组关联研究。我们预计将在 10 月份收到该项目的遗传数据。由于这些都是相当大规模的工作，计算需求将是巨大的，就效率而言超出了我们当前的能力。