A Collaborative Genomic Study of Bipolar Disorder

双相情感障碍的合作基因组研究

• 批准号: 6989088
• 负责人: John P. Rice
• 金额: $ 37.35万
• 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/6989088
• 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遗传学倡议一直支持双相情感障碍（BP）研究的国家资源。到1997年，153个多重家庭进行了评估，提供细胞系，DNA和匿名的临床数据。现在这是一个公开的资源，分析结果已经公布。第二次努力开始于1998年，以确定500个新的BP同胞对，这一目标已经超过了523个额外的BPI同胞对确定，采访，并收集DNA样本。遗传疾病研究中心已完成了对237个同胞对家庭的全基因组扫描，其余309个家庭将在2003年期间由CIDR进行基因分型。这是同类中最大的资源，揭示了染色体6q和17q上连锁区域的证据。它还提供了染色体22q上的一个位点的确认，并支持1p，10p，16p，13q和21q上的区域。累积的连锁数据已经涉及到其他染色体区域。我们建议扩展国家遗传资源，包括5000个无关的BP先证者和2000个父母的病例对照和以家庭为基础的关联研究的样本。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11个研究中心进行确定和评估（之前参与的10个研究中心加上霍华德大学，该大学将提供非裔美国人先证者）。这个样本将是一个全国性的资源，用于连锁区域内的精细连锁不平衡作图，以及候选基因关联研究。子样本中的父母DNA将允许控制种族分层。生物信息学技术将被开发和支持，用于候选区域的基因组分析，以帮助选择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个实验室之间进行协调，采用明智的逐步方法，首先对当前699个家系进行标准微卫星定位，然后在工业实验室进行SNP合同基因分型，并继续在各个研究中心的实验室进行后续基因分型和候选基因和区域测序。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。分析现有的同胞对家庭加上这一大套的情况下，控制应允许确认几个脆弱性基因在此期间的补助金。