Collaborative Genomic Study of Bipolar Disorder

双相情感障碍的合作基因组研究

• 批准号: 7173388
• 负责人: John R. Kelsoe
• 金额: $ 38.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7173388
• 关键词: 10p; 13q; 16p; 17q; 21q; 22q; Affect; African American; Area; Bioinformatics; Biological; Bipolar Disorder; Candidate Disease Gene; Cell Line; Cells; Chromosomes; Clinical Data; Companions; Contracts; DNA; DNA Databases; Data; Data Linkages; Data Sources; Databases; Deposition; Diagnostic; Disease; Enrollment; Evaluation; Extramural Activities; Family; Funding; Genes; Genetic; Genomics; Genotype; Goals; Grant; Haplotypes; Individual; Inherited; Interview; Intramural Research Program; Laboratories; Linkage Disequilibrium Mapping; Maps; Methods; Microsatellite Repeats; Modeling; Molecular Genetics; Mood Disorders; National Institute of Mental Health; Parents; Phenotype; Polymorphic Microsatellite Marker; Predisposition; Protocols documentation; Publications; Publishing; Qualifying; Relative Risks; Reporting; Research; Research Personnel; Resource Sharing; Resources; Rice; Risk; SNP genotyping; Sample Size; Sampling; Siblings; Site; Standards of Weights and Measures; Stratification; Study Subject; Techniques; Training; Triad Acrylic Resin; Universities; Update; Variant; Work; base; case control; cohort; data integration; data mining; design; family genetics; follow-up; genetic linkage analysis; genetic pedigree; genetic resource; genome wide association study; interest; lymphoblastoid cell line; positional cloning; proband; programs; repository; scaffold; size; tool

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遗传学倡议支持了双相情感障碍研究的国家资源（BP）。到1997年，评估了153个多重家族，提供细胞系，DNA和匿名临床数据。现在，这是一种公开可用的资源，并且已经发布了分析结果。 1998年开始了第二次努力，以确定500个新的BP SIB对，并且该目标已超过523个额外的BPI SIB对确定，采访，并收集了DNA样品。在遗传性疾病研究中心（CIDR）对237个SIB对家族（CIDR）进行了一项基因组广泛的扫描，其余的309个家族将由CIDR在2003年期间进行基因分型。这种资源是此类资源，这是同类产品中最大的资源，揭示了关于染色体6q和17q染色体上连接领域的证据。它还提供了对22q染色体染色体上的基因座的确认，并为1p，10p，16p，13q和21q的面积提供了支持。累积的连锁数据牵涉到其他染色体区域。我们建议将国家遗传资源扩展，以包括5000个无关的BP Probands和2000个病例对照的父母和基于家庭的关联研究的样本。控制样本将通过NIMH遗传学计划国家资源获得。将在11个地点（以前参与的十个站点加霍华德大学（将为非裔美国人的证据）中确定和评估证据和父母。该样本将是在连锁区域内以及候选基因协会研究中进行精细链接不平衡映射的国家资源。子样本中的父母DNA将允许控制种族分层。将开发和支持生物信息学技术，用于候选区域的基因组分析，以帮助选择SNP和其他多态标记物（包括周围和候选基因）和底漆设计。基因分型将在8个实验室中以知情的阶梯方法进行协调，从标准的微卫星映射开始，对当前的699个血统组的标准映射开始，然后是工业实验室中SNP的合同基因分型，然后继续进行候选基因和各个位置的候选基因和区域的后续基因分型和测序。较大的病例对照样本的SNP键入将发生在协作研究的最后一年。对现有的SIB对家族的分析以及此大量病例和控制措施应允许在此赠款期间确认几个漏洞基因。

项目成果

A genome-wide association study of bipolar disorder and comorbid migraine.

• DOI: 10.1111/j.1601-183x.2010.00601.x
• 发表时间: 2010-10
• 期刊: Genes, brain, and behavior
• 作者: Oedegaard KJ;Greenwood TA;Johansson S;Jacobsen KK;Halmoy A;Fasmer OB;Akiskal HS;Bipolar Genome Study (BiGS);Haavik J;Kelsoe JR
• 通讯作者: Kelsoe JR

Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis.

• DOI: 10.1016/j.biopsych.2016.08.040
• 发表时间: 2017-11-01
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: van Hulzen KJE;Scholz CJ;Franke B;Ripke S;Klein M;McQuillin A;Sonuga-Barke EJ;PGC ADHD Working Group;Kelsoe JR;Landén M;Andreassen OA;PGC Bipolar Disorder Working Group;Lesch KP;Weber H;Faraone SV;Arias-Vasquez A;Reif A
• 通讯作者: Reif A

Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.

• DOI: 10.1038/ng.523
• 发表时间: 2010-02
• 期刊: Nature genetics
• 影响因子: 30.8