A Collaborative Genomic Study of Bipolar Disorder

双相情感障碍的合作基因组研究

• 批准号: 7183495
• 负责人: John P. Rice
• 金额: $ 36.27万
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7183495
• 关键词: 10p; 13q; 16p; 17q; 21q; 22q; Affect; African American; Area; Bioinformatics; Biological; Bipolar Disorder; Candidate Disease Gene; Cell Line; Chromosomes; Clinical Data; Companions; Contracts; DNA; DNA Databases; Data; Data Linkages; Data Sources; Databases; Deposition; Diagnostic; Disease; 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; Research; Research Personnel; Resource Sharing; Resources; 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; 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遗传学倡议一直支持一个研究双相情感障碍(BP)的国家资源。到1997年，对153个多基因家系进行了评估，提供了细胞系、DNA和匿名的临床数据。这现在是一个公开可用的资源，分析结果已经公布。1998年开始了第二项工作，以确定500个新的BP同胞对，这一目标已经超过了这一目标，确定了另外523个BPI同胞对，进行了访谈，并收集了DNA样本。遗传病研究中心(CIDR)已经完成了对237个同胞对家庭的全基因组扫描，其余309个家庭将在2003年期间通过CIDR进行基因分型。这个资源是同类资源中最大的，它揭示了6q和17q染色体上的连锁区的证据。它还证实了染色体22q上的一个基因座，并支持1p、10p、16p、13q和21q上的区域。不断积累的连锁数据还牵涉到其他染色体区域。我们建议扩大国家遗传资源的范围，包括5000名无血缘关系的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11个地点进行确定和评估(之前参与的10个地点加上将提供非裔美国人先证者的霍华德大学)。这一样本将成为在连锁区域内进行精细连锁不平衡定位以及候选基因关联研究的全国性资源。子样本中的父母DNA将允许对种族分层进行控制。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SNPs和其他多态标记(包括周围和候选基因内)，以及引物设计。基因分型将在8个实验室以知情的循序渐进的方法进行协调，首先是对当前的699个家系进行标准微卫星图谱绘制，然后是在一个工业实验室对SNPs进行合同基因分型，然后继续在各个地点的实验室对候选基因和区域进行后续基因分型和排序。对较大的病例对照样本进行SNP分型将在合作研究的最后一年进行。对现有同胞配对家庭的分析，加上这一大组病例和对照，应该能够在这一赠款期间确认几个易受感染的基因。

项目成果

Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

• DOI: 10.1016/s0140-6736(16)00143-4
• 发表时间: 2016-03-12
• 期刊: Lancet (London, England)
• 作者: Hou L;Heilbronner U;Degenhardt F;Adli M;Akiyama K;Akula N;Ardau R;Arias B;Backlund L;Banzato CEM;Benabarre A;Bengesser S;Bhattacharjee AK;Biernacka JM;Birner A;Brichant-Petitjean C;Bui ET;Cervantes P;Chen GB;Chen HC;Chillotti C;Cichon S;Clark SR;Colom F;Cousins DA;Cruceanu C;Czerski PM;Dantas CR;Dayer A;Étain B;Falkai P;Forstner AJ;Frisén L;Fullerton JM;Gard S;Garnham JS;Goes FS;Grof P;Gruber O;Hashimoto R;Hauser J;Herms S;Hoffmann P;Hofmann A;Jamain S;Jiménez E;Kahn JP;Kassem L;Kittel-Schneider S;Kliwicki S;König B;Kusumi I;Lackner N;Laje G;Landén M;Lavebratt C;Leboyer M;Leckband SG;Jaramillo CAL;MacQueen G;Manchia M;Martinsson L;Mattheisen M;McCarthy MJ;McElroy SL;Mitjans M;Mondimore FM;Monteleone P;Nievergelt CM;Nöthen MM;Ösby U;Ozaki N;Perlis RH;Pfennig A;Reich-Erkelenz D;Rouleau GA;Schofield PR;Schubert KO;Schweizer BW;Seemüller F;Severino G;Shekhtman T;Shilling PD;Shimoda K;Simhandl C;Slaney CM;Smoller JW;Squassina A;Stamm T;Stopkova P;Tighe SK;Tortorella A;Turecki G;Volkert J;Witt S;Wright A;Young LT;Zandi PP;Potash JB;DePaulo JR;Bauer M;Reininghaus EZ;Novák T;Aubry JM;Maj M;Baune BT;Mitchell PB;Vieta E;Frye MA;Rybakowski JK;Kuo PH;Kato T;Grigoroiu-Serbanescu M;Reif A;Del Zompo M;Bellivier F;Schalling M;Wray NR;Kelsoe JR;Alda M;Rietschel M;McMahon FJ;Schulze TG
• 通讯作者: Schulze TG

Clinical features of bipolar disorder comorbid with anxiety disorders differ between men and women.

男性和女性的躁郁症合并症与焦虑症的临床特征不同。

• DOI: 10.1002/da.21932
• 发表时间: 2012-08
• 期刊: DEPRESSION AND ANXIETY
• 影响因子: 7.4
• 作者: Saunders, Erika F. H.;Fitzgerald, Kate D.;Zhang, Peng;McInnis, Melvin G.
• 通讯作者: McInnis, Melvin G.

Rapid switching of mood in families with familial bipolar disorder.

患有家族性双相情感障碍的家庭的情绪快速转变。

• DOI: 10.1111/j.1399-5618.2008.00600.x
• 发表时间: 2008
• 期刊: Bipolar disorders
• 影响因子: 5.4
• 作者: Nwulia,EvaristusA;Zandi,PeterP;McInnis,MelvinG;DePauloJr,JRaymond;MacKinnon,DeanF
• 通讯作者: MacKinnon,DeanF

Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder.

• DOI: 10.1038/mp.2008.134
• 发表时间: 2009-05
• 期刊: Molecular psychiatry
• 影响因子: 11

Circadian polymorphisms associated with affective disorders.

• DOI: 10.1186/1740-3391-7-2
• 发表时间: 2009-01-23
• 期刊: Journal of circadian rhythms
• 作者: Kripke DF;Nievergelt CM;Joo E;Shekhtman T;Kelsoe JR
• 通讯作者: Kelsoe JR