THE GENETIC DETERMINANTS OF BIPOLAR DISORDER AND SCHIZOPHRENIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 事实证明，发现易患复杂疾病的基因，如双相情感障碍和精神分裂症，是非常困难的。多年来，基因组连锁扫描已经确定了一些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温和性质和它们所包含的广泛的遗传区域，这可能是众所周知的与双相情感障碍、精神分裂症和精神疾病相关的临床和遗传异质性的结果。研究人员现在转向了替代策略，如使用内表型、候选基因研究和大规模基因组关联研究，希望这些方法可能有助于复杂疾病的遗传解剖。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。我们还将在我们的遗传网络分析结果的指导下进行基因-基因相互作用研究。此外，作为NIMH双相情感障碍遗传学倡议的一部分，我们将继续进行双相情感障碍及其相关表型的全基因组关联研究，该倡议正在参与由遗传协会信息网络(GAIN)发起的基因鉴定倡议。我们预计将在10月份收到该项目的基因数据。由于这些都是相当大的努力，计算需求将是巨大的，超过了我们目前的能力，就效率而言。

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.