A Collaborative Genomic Study of Bipolar Disorder

双相情感障碍的合作基因组研究

• 批准号: 7312916
• 负责人: Francis J McMahon
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7312916
• 关键词: Collaborative; Genomic; Study; Bipolar; Disorder

Since 1988 the NIMH Genetics Initiative has supported a national resource for the study of bipolar disorder (BP). By 1997 153 multiplex families were assessed, providing cell lines, DNA, and anonymized clinical data. This is now a publicly available resource and analytic results have been published. A second effort commenced in 1998 to ascertain 500 new BP sib pairs and this goal has been exceeded with 523 additional BPI sib pairs ascertained, interviewed, and a DNA sample collected. A genome wide scan has been completed at the Center for Inherited Disease Research (CIDR) on 237 sib pair families and the remaining 309 families was genotyped by CIDR during 2003. This resource, the largest of its kind, has revealed evidence for areas of linkage on chromosomes 6q and 17q. It has also provided confirmation of a locus on chromosome 22q and support for areas on 1p, 10p, 16p, 13q, and 21q. Accumulating linkage data has implicated other chromosomal regions. This extension of the national genetic resource will include a sample of 5000 unrelated BP probands and 2000 parents for case-control, and family-based association studies. Control samples will be obtained through the NIMH Genetics Initiative national resource. Probands and parents will be ascertained and assessed at eleven sites (the ten sites previously participating plus Howard University, which will provide African-American probands). Parental DNAs in a subsample will allow control for ethnic stratification. This sample will be a national resource for fine scale linkage disequilibrium mapping within regions of linkage, as well as candidate gene association studies. In the past year, we have succeeded in identifying, through a combined analysis of this sample and several other family samples, the first genome-wide significant linkages in bipolar disorder (McQueen et al 2005). The strongest linkage, on chromosome 6q, corresponds to a region first implicated in the NIMH Wave 3 families (Dick et al 2003), which has been a major focus of this Unit ever since. A major related project, known as the Bipolar Disorder Phenome Project, aims to collate all of the clinical data collected from all 4000+ participants in the Genetics Initiative study that have been enrolled since 1992. So far we have compiled and verified data on over 2000 variables, accounting for changes in the collection instruments and diagnostic criteria over the last 13 years. This database, which will be released to the scientific community in 2007, will be a major resource for researchers in the field of bipolar disorder.

自 1988 年以来，NIMH 遗传学计划一直支持双相情感障碍 (BP) 研究的国家资源。到 1997 年，我们对 153 个多重家族进行了评估，提供了细胞系、DNA 和匿名临床数据。现在这是一个公开可用的资源，并且分析结果已经发布。第二次工作于 1998 年开始，旨在确定 500 个新的 BP 同胞对，并通过确定、访谈并收集了 523 个额外的 BPI 同胞对，超出了这一目标。遗传病研究中心 (CIDR) 已完成了对 237 个同胞对家族的全基因组扫描，其余 309 个家族在 2003 年由 CIDR 进行了基因分型。这一资源是同类资源中规模最大的，揭示了关联领域的证据位于 6q 和 17q 染色体上。它还确认了染色体 22q 上的基因座，并支持 1p、10p、16p、13q 和 21q 上的区域。积累的连锁数据暗示了其他染色体区域。国家遗传资源的扩展将包括 5000 名无关的 BP 先证者和 2000 名父母的样本，用于病例对照和基于家庭的关联研究。对照样本将通过 NIMH 遗传学倡议国家资源获得。先证者和父母将在十一个地点进行确定和评估（之前参与的十个地点加上霍华德大学，该大学将提供非裔美国先证者）。子样本中的亲本 DNA 将允许控制种族分层。该样本将成为连锁区域内精细连锁不平衡图谱以及候选基因关联研究的国家资源。 在过去的一年中，通过对该样本和其他几个家族样本的综合分析，我们成功地确定了双相情感障碍中第一个全基因组范围内的显着联系（McQueen 等，2005）。染色体 6q 上最强的连锁对应于首先涉及 NIMH Wave 3 家族的区域（Dick 等人 2003），此后该区域一直是本单元的主要焦点。 一个重要的相关项目称为双相情感障碍表型组项目，旨在整理从 1992 年以来注册的遗传学倡议研究中所有 4000 多名参与者收集的所有临床数据。到目前为止，我们已经汇编并验证了 2000 多个参与者的数据变量，解释了过去 13 年收集工具和诊断标准的变化。该数据库将于 2007 年向科学界发布，将成为躁郁症领域研究人员的主要资源。