GENETICS OF RECURRENT EARLY ONSET DEPRESSION

描述：(改编自研究人员摘要)严重抑郁障碍 (MDD)至少有5%-10%的终生人口流行率，并导致严重的 发病率和死亡率，包括自杀。双胞胎遗传力在0.4-0.70之间。 对复发、早发的患者进行易感基因定位可能是可行的 亚型(MDD-RE)，其患病风险增加三到八倍 先证者的一级亲属，与所有MDD的双重亲属。情结 传播模式提示多基因传播和/或基因座 异质性，因此可能需要大样本。我们提议一项为期四年的 六个地点项目，收集估计770个家系，包含1,000个 独立受影响的兄弟姐妹对(ASP)，扩展一次 包括其他受影响的亲属以及未受影响的亲属的关系 亲属(父母和兄弟姐妹)获取遗传期信息。所有站点都将拥有 相同的纳入标准、临床评估摘要和无花果访谈以及 NEO个性问卷)、面试官培训和可靠性 监测、协商一致诊断程序、数据管理系统和 行政监督，包括质量保证计划。永久性细胞 将在NIMH赞助的细胞中创建品系样本并提取DNA 存储库。对所有受影响的受试者进行10 cM的基因组扫描 遗传病研究中心(CIDR)已经批准了这一点 CIDR访问的项目。提出了一种三阶段设计：区域最大 超过自由模拟门槛的LOD分数(MLS)将为 在年上半年对受影响个人的基因组扫描中发现的 样本，以及继续满足此条件的选定候选区域 在这些区域中键入未受影响的个人并添加到 分析。这些地区存在联系的证据随后将在 使用Strigent进行参数分析和非参数分析的整个样本 基于模拟的阈值为5%的全基因组意义。在四年中 在项目期内，可以完成80%的样本的遗传分析(超过 600个家系，800个ASP)，其余的家系将由 项目期结束，立即完成对这些病毒的基因组扫描 CIDR的家谱。 为快速共享所有生物材料提出了一个时间表，是盲目的 临床数据、基因分型和与科学界的连锁分析 通过NIMH赞助的遗传研究中心。

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.