GENETICS OF RECURRENT EARLY ONSET DEPRESSION

复发性早发性抑郁症的遗传学

• 批准号: 6039529
• 负责人: WILLIAM A SCHEFTNER
• 金额: $ 27.66万
• 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/6039529
• 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：（改编自研究者的摘要）重度抑郁症 (MDD) 的终生人口患病率至少为 5-10%，并会导致严重的 发病率和死亡率，包括自杀。双胞胎的遗传力为0.4-0.70。 对于复发性、早发型的疾病，绘制易感基因图谱可能是可行的 亚型（MDD-RE），其风险增加三到八倍 先证者的一级亲属，而所有 MDD 的一级亲属。综合体 传播模式表明多基因传播和/或多基因座 异质性，因此可能需要大样本。我们建议为期四年， 六个地点的项目，收集估计 770 个谱系图，其中包含 1,000 个谱系图 独立受影响的兄弟姐妹对 (ASP)，按一级扩展 关系包括其他受影响的亲属以及未受影响的亲属 亲属（父母和兄弟姐妹）获取遗传阶段信息。所有站点都会有 相同的纳入标准、临床评估 DIGS 和 Figs 访谈以及 NEO 性格量表）、访谈员培训和可靠性 监测、共识诊断程序、数据管理系统，以及 行政监督，包括质量保证计划。永久细胞 将在 NIMH 赞助的细胞中制作细胞系样本并提取 DNA 存储库。所有受影响受试者的 10 cM 基因组扫描将于 遗传病研究中心 (CIDR) 已批准此 CIDR 访问项目。提出了三阶段设计：具有最大 lod 分数 (MLS) 超过基于自由模拟的阈值将 上半年受影响个体的基因组扫描中发现 样本和选择的候选区域继续满足这一要求 在这些区域中输入未受影响的个体并将其添加到后的阈值 分析。这些区域之间联系的证据将在 使用严格的参数和非参数分析整个样本 基于模拟的 5% 全基因组显着性阈值。在这四年里 项目期间，可完成80%样本的遗传分析（超过 600 个血统，800 个 ASP），其余家族由 项目期结束后立即完成对这些基因组的扫描 CIDR的血统书。 提出了快速共享所有生物材料的时间表，盲法 临床数据、基因型以及与科学界的连锁分析 通过 NIMH 资助的基因研究中心。