GENETICS OF RECURRENT EARLY ONSET DEPRESSION

复发性早发性抑郁症的遗传学

• 批准号: 6528536
• 负责人: WILLIAM A SCHEFTNER
• 金额: $ 28.17万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6528536
• 关键词: behavioral genetics; clinical research; cooperative study; disease /disorder onset; family genetics; genetic mapping; genetic susceptibility; genotype; human genetic material tag; human subject; major depression; phlebotomy

DESCRIPTION: (Adapted from investigator's abstract) Major depressive disorder (MDD) has at least a 5-10% lifetime population prevalence and causes severe morbidity and mortality including suicide. Heritability in twins is 0.4-0.70. Mapping of susceptibility genes may be feasible with the recurrent, early-onset subtype (MDD-RE) which demonstrates a three- to eight-fold increase in risk to first-degree relatives of probands, vs. twofold for all MDD. The complex pattern of transmission suggests multigenic transmission and/or locus heterogeneity, so that large samples may be required. We propose a four-year, six-site project to collect an estimated 770 pedigrees which contain 1,000 independent affected sibling pairs (ASPs), extended by first-degree relationships to include additional affected relatives, plus unaffected relatives (parents and sibs) for genetic phase information. All sites will have identical inclusion criteria, clinical assessment DIGS and FIGS interviews and the NEO personality inventory), interviewer training and reliability monitoring, consensus diagnostic procedures, data management system, and administrative oversight including a quality assurance program. Permanent cell line specimens will be created and DNA extracted at the NIMH-sponsored cell repository. A 10 cM genome scan will be completed on all affected subjects at the Center for Inherited Disease Research (CIDR), which has approved this project for CIDR access. A three-stage design is proposed: regions with maximum lod scores (MLS) exceeding a liberal simulation-based threshold will be identified in a genome scan of the affected individuals from the first half of the sample, and candidate regions selected which continue to meet this threshold after unaffected individuals are typed in these regions and added to the analysis. Evidence for linkage in these regions will then be tested in the entire sample with parametric and non-parametric analyses using stringent simulation-based thresholds for 5% genome-wide significance. In the four-year project period, genetic analyses can be completed on 80% of the sample (over 600 pedigrees, 800 ASPs), with the remaining families to be available by the end of the project period for immediate completion of the genome scan on these pedigrees at CIDR. A timetable is proposed for rapid sharing of all biological materials, blinded clinical data, genotypes and linkage analyses with the scientific community through the NIMH-sponsored Center for Genetic Studies.

描述：（改编自研究者摘要）重度抑郁症 (MDD)至少有5-10%的终生人口患病率，并造成严重的 发病率和死亡率，包括自杀。双胞胎的遗传度为0.4-0.70。 易感基因的定位可能是可行的复发性，早发性 亚型（MDD-RE），表现出三至八倍的风险增加， 先证者的一级亲属，而所有MDD的一级亲属为两级亲属。复杂 传播模式提示多基因传播和/或位点 不均匀性，因此可能需要大样本。我们提议一个四年期， 六个地点的项目将收集估计770个谱系，其中包含1，000个 独立受累同胞对（ASP），一级扩展 包括其他受影响的亲属，以及未受影响的亲属 亲属（父母和同胞）的遗传相位信息。所有研究中心都将 相同的入选标准，临床评估DIGS和FIGS访谈， NEO人格调查表）、访谈者培训和可靠性 监测、共识诊断程序、数据管理系统，以及 包括质量保证计划在内的行政监督。永久细胞 将在NIMH赞助的细胞中创建细胞系标本并提取DNA 仓库。所有受影响的受试者将完成10 cM基因组扫描， 遗传疾病研究中心（CIDR）批准了这项研究。 项目CIDR访问。提出了三阶段设计：最大值区域 超过自由模拟阈值的lod分数（MLS）将被 在2009年上半年受影响个体的基因组扫描中发现， 所选择的样本和候选区域继续满足该 阈值后，未受影响的个人在这些地区分型，并添加到 的分析。这些地区的联系证据将在 整个样本的参数和非参数分析，使用严格的 5%全基因组显著性的基于模拟的阈值。技 在项目期间，可以对80%的样本（超过 600个家系，800个ASP），其余的家庭将由 在项目期结束后立即完成对这些人的基因组扫描， 在CIDR的家谱。 提出了快速共享所有生物材料的时间表， 临床数据、基因型和与科学界的关联分析 通过NIMH赞助的遗传研究中心。