Genetics of Early-Onset Depression

早发性抑郁症的遗传学

基本信息

批准号：
7476566
负责人：
WILLIAM Bradford LAWSON
金额：
$ 25.26万
依托单位：
HOWARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-22 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7476566
关键词：
15q 17p 18q Adult Affect African African American Bioinformatics Biological Blinded Blood specimen Candidate Disease Gene Case-Control Studies Cell Line Cells Child Abuse Chromosomes Clinical Clinical Data Collection Cultured Cells Data Databases Deposition Diagnosis Diagnostic Disease Ethnic Origin European Family Family history of Genes Genetic Genome Genome Scan Genotype Individual Interview Investigation Lead Linkage Disequilibrium Linkage Disequilibrium Mapping Location Major Depressive Disorder Maps Mental Depression Methods Minority Modeling National Institute of Mental Health Parents Phenotype Platelet Factor 4 Predisposition Recruitment Activity Recurrence Relative (related person)Research Design Research Personnel Risk Factors SNP genotyping Sampling Sampling Studies Series Siblings Single Nucleotide Polymorphism Map Site Susceptibility Gene Universities Validation base case control chromosome 5q loss early childhood early onset follow-up genetic pedigree indexing male neglect positional cloning proband repository research study sex

项目摘要

DESCRIPTION (provided by applicant): This is a second revision of a collaborative R01 four-year competing continuation proposal to create a large repository-based sample of cases with recurrent, early-onset major depressive disorder (MDD-RE), and to use positional cloning to identify depression susceptibility genes in regions of significant linkage in our genome scan. The completed four-year project collected 680 families containing 927 affected sibling pairs (ASPs) (MDD-RE diagnostic model) and additional affected relatives (GenRED I). Blinded clinical data and blood specimens for cell culture were deposited in the NIMH repository and are being made public. Linkage fine-mapping has demonstrated genome-wide significant linkage on chromosome 15q; in the 10 cM genome scan, suggestive sex-specific linkage was observed in three regions (6p-q, 8p, 17p), with the result on chromosome 17p approaching genome-wide significance. Six collaborating sites now propose to: (1) Collect (during Years 1-3) an additional 1,350 European-ancestry (EUR) MDD-RE probands (GenRED II) meeting identical criteria (including evidence of having an affected sibling) to create a total repository sample of 2,000 EUR MDD-RE cases, plus cell lines/DMA from available parents, unaffected sibs and male-male ASPs. (2) Initiate a repository-based collection of African-American (AA) MDD-RE probands meeting the same clinical criteria. We will collect 750 AA probands plus available parents and affected siblings, with involvement of young minority co-investigators; AA controls will be available from the repository. A site at Howard University has been added to lead this effort. AA recruitment will continue through Year 4 to build the repository sample. (3) Collect data on childhood abuse and neglect and parental loss, major environmental MOD risk factors; (4) Carry out linkage fine-mapping studies of chromosomes 17p, 1q, 5q, 6p-q, 8p and 18q to maximize evidence for linkage and to narrow candidate regions. (5) Carry out linkage disequilibrium (LD) mapping and intensive gene analysis studies in the 15q candidate region and one additional region in 2,000 EUR cases and 2,000 screened, ethnically-matched controls; and carry out LD fine-mapping studies in the most significant genes in 600 AA cases (the N available early in Year 4) and 1,000 controls, using high-throughput SNP genotyping methods, to identify a depression susceptibility gene. The proposed studies will contribute to the understanding of this devastating common disorder by identifying susceptibility genes, and by creating a public collection of biological materials and clinical data, as well as over 13 million SNP genotypes, to facilitate further investigation of recurrent MOD and related phenotypes.

描述（由申请人提供）：这是协作R01的四年竞争持续建议的第二次修订，以创建一个大型基于存储库的案例样本，以复发，早期发作的主要抑郁症（MDD-RE），并使用位置克隆以鉴定我们基因组扫描中显着连锁区域中抑郁敏感性基因。完整的四年项目收集了680个家庭，其中包含927个受影响的兄弟姐妹对（ASP）（MDD-RE诊断模型）和其他受影响的亲戚（Genred I）。盲目的临床数据和用于细胞培养的血液样本被沉积在NIMH存储库中，并被公开。链接细映射已显示在染色体15Q上的全基因组显着连接；在10 cm的基因组扫描中，在三个区域（6p-q，8p，17p）中观察到了暗示性的性别特异性连接，结果是17p染色体接近全基因组意义的结果。六个合作网站现在建议：（1）（在1 - 3年内）额外收集1,350个欧洲委员会（EUR）MDD-RE Probands（Genred II）符合相同标准（包括具有影响兄弟姐妹的证据），以创建2,000 EUR MDD的总存储库样本 - RE病例，以及可用父母的细胞系/DMA，未受影响的SIB和男性ASP。（2）启动基于存储库的非洲裔美国人（AA）MDD-RE检验，符合相同的临床标准。我们将收集750个AA概率，以及可用的父母和受影响的兄弟姐妹，并与年轻的少数民族共同研究员有关； AA控件将从存储库中获得。添加了霍华德大学的一个网站以领导这项工作。 AA招聘将持续到4年级，以建立存储库样本。（3）收集有关儿童虐待，忽视和父母损失的数据，主要环境国防部的风险因素；（4）对染色体17p，1q，5q，5q，6p-Q，8p和18Q进行连锁细图研究，以最大程度地证明连锁和狭窄的候选区域。（5）在15Q候选区域进行连锁不平衡（LD）映射和密集的基因分析研究，并在2,000欧元的案例和2,000个筛选，种族匹配的对照中进行另外一个区域；并使用高通量SNP基因分型方法在600例AA病例中对最重要的基因进行LD精细映射研究，并进行1,000个对照。拟议的研究将通过识别易感性基因，并创建生物材料和临床数据的公共收集以及超过1300万SNP基因型来帮助理解这种毁灭性常见疾病的理解，以促进对经常性mod和相关表型的进一步研究。。