A Collaborative Genomic Study of Bipolar Disorder

双相情感障碍的合作基因组研究

• 批准号: 6720903
• 负责人: John P. Rice
• 金额: $ 38.25万
• 依托单位: WASHINGTON UNIVERSITY
• 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 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6720903
• 关键词: behavioral genetics; bioinformatics; bipolar depression; cell line; clinical research; cooperative study; cryopreservation; disease /disorder etiology; family genetics; functional /structural genomics; gene expression; gene frequency; genetic disorder; genetic markers; genetic registry /resource /referral center; genetic susceptibility; genotype; human genetic material tag; human subject; interview; linkage disequilibriums; linkage mapping; mental disorder diagnosis; nucleic acid sequence; polymerase chain reaction; siblings; single nucleotide polymorphism

DESCRIPTION (provided by applicant): 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 will be 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. We propose an extension of the national genetic resource to 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). This sample will be a national resource for fine scale linkage disequilibrium mapping within regions of linkage, as well as candidate gene association studies. Parental DNAs in a subsample will allow control for ethnic stratification. Bioinformatics techniques will be developed and supported for genomic analysis of candidate regions, to assist selection of SNPs and other polymorphic markers (including surrounding and within candidate genes), and primer design. The genotyping will be coordinated across 8 labs with an informed step-wise approach, beginning with standard microsatellite mapping of the current set of 699 pedigrees, followed by contract genotyping of SNPs in an industrial laboratory, and continuing with follow-up genotyping and sequencing of candidate genes and regions in laboratories at the individual sites. SNP typing of the larger case-control sample will occur in the final year of the collaborative study. Analysis of the existing sib pair families plus this large set of cases and controls should permit the confirmation of several vulnerability genes during this grant period.

描述（由申请人提供）：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) 已经完成了对 237 个同胞对家族的全基因组扫描，其余 309 个家族将在 2003 年由 CIDR 进行基因分型。这一资源是同类资源中规模最大的，已揭示了染色体 6q 和 17q 上连锁区域的证据。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。我们建议扩大国家遗传资源，纳入 5000 名无关的 BP 先证者和 2000 名父母的样本，以进行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）。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。子样本中的亲本 DNA 将允许控制种族分层。将开发和支持候选区域的基因组分析的生物信息学技术，以协助选择 SNP 和其他多态性标记（包括候选基因周围和内部）以及引物设计。基因分型将在 8 个实验室之间采用明智的逐步方法进行协调，首先对当前 699 个谱系进行标准微卫星图谱，然后在工业实验室中对 SNP 进行合同基因分型，并继续在各个地点的实验室中对候选基因和区域进行后续基因分型和测序。较大病例对照样本的 SNP 分型将在合作研究的最后一年进行。对现有同胞对家庭的分析加上这一大组病例和对照应该可以在本资助期间确认几个易受攻击的基因。