GENETIC EPIDEMIOLOGY OF ALZHEIMER DISEASE IN TWINS

双胞胎阿尔茨海默病的遗传流行病学

• 批准号: 2429267
• 负责人: John C S Breitner
• 金额: $ 93.93万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-04 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2429267
• 关键词: Alzheimer's disease; aging; apolipoprotein E; clinical research; disease /disorder proneness /risk; dizygotic twins; family genetics; gene environment interaction; gene expression; genotype; human population genetics; human subject; interview; longitudinal human study; molecular pathology; monozygotic twins; nervous system disorder epidemiology; neurogenetics; patient /disease registry; prognosis; twin /multiplet; veterans

DESCRIPTION: (Adapted from Investigator's Abstract) The National Academy of Sciences - National Research Council Registry of aging twin veterans ("the Registry") contains 6,000 living pairs of white male twins who will be aged 68-80 in 1996-97. This extensively revised application proposes studies in the Registry that, combined with work to date, will yield 130 twin pairs with Alzheimer's disease (AD). That population-based panel will enable the continued investigation of three broad aims: 1) evaluation of genetic causes of AD by contrasting the similarity of onsets within monozygotic (MZ) and dizygotic (DZ) pairs, and within age-matched pairs of unrelated individuals; 2) characterization of the environmental contribution to variability of onset of AD; (for example, variability of onset within MZ pairs defines the maximum degree to which environmental influences can modify the onset of AD); and 3) identification of specific factors associated with accelerated onset of AD, using the co-twin control method. The research will capitalize upon recent developments in the genetics of AD. Genotype at the locus for apolipoprotein E (APOE) influences both liability to AD and its timing of onset. Other similar genetic systems may soon be identified. Such findings enable the incorporation of refinements into the classical twin paradigm of investigating broad (but heterogeneous) genetic and environmental influences. Thus, the investigators state that one can not only estimate the heritability of AD in general, but also undertake partitioned analyses to estimate the phenotypic variance to genotypes at APOE or other marker systems, as these are identified, and to still other (unknown) genes that predispose to AD. Several MZ twin pairs have been described with widely divergent onsets of AD. Environmental factors may therefore alter the onset, and hence the population risk, of some genetically defined forms of AD. This study will analyze the environmental contribution to variability of onset, and will characterize the divergence in onset within sets of genetically matched individuals. It will also employ the co-twin control method to seek the specific environmental factors that may be responsible for this variation. Because the AD cases here will typically have experienced a relatively early onset (given their genotype), the investigators will concentrate on factors that accelerate the onset of AD. Reduction in population exposure to such factors could result in a dramatic decrease in the public health burden of AD. The investigators state that a population-based twin design remains the ideal approach to these sorts of investigations, but the cost of such studies is a concern. They further state that alterations to the current work plan have resulted in a budget reduction of 19.2%, as compared wit the prior application.

描述：（改编自研究者摘要）美国国家科学院 科学-国家研究理事会登记处的老年双胞胎退伍军人（“ 登记处”）包含6,000对活着的白色男性双胞胎， 1996-97年为68-80。 这一广泛修订的申请建议研究， 登记处，结合迄今为止的工作，将产生130对双胞胎 阿尔茨海默病（AD） 这一基于人口的小组将使 继续研究三个广泛的目标：1）遗传学评价 通过对比单合子（MZ）内发病的相似性， 和双合子（DZ）对，以及年龄匹配的不相关对 2）环境贡献的特征， AD发作的变异性;（例如，MZ内发作的变异性 pairs定义了环境影响的最大程度 改变AD的发作）;和3）识别特定因素 与AD的加速发作相关，使用双胞胎对照方法。 这项研究将利用AD遗传学的最新发展。 载脂蛋白E（APOE）基因座的基因型影响这两种倾向 AD及其发病时间。 其他类似的遗传系统可能很快就会 鉴定 这些发现使得能够将改进纳入 研究广泛（但异质）遗传的经典双生子范式 和环境影响。 因此，研究人员表示，人们可以 不仅从总体上估计了AD的遗传度， 分区分析，以估计基因型的表型方差， APOE或其他标记系统，因为这些被识别，并且还涉及其他标记系统。 （未知）易患AD的基因。 几个MZ双胞胎对已经被描述为具有广泛不同的起始点， AD. 因此，环境因素可能会改变发病， 人群风险，一些遗传定义的AD形式。 本研究将 分析环境对发病变异性的影响，并将 描述基因匹配的多组患者中发病的差异 个体 它还将采用共孪生控制方法来寻求 可能导致这种变化的特定环境因素。 因为这里的AD病例通常会经历相对较早的 发病（鉴于他们的基因型），研究人员将集中在因素 加速AD的发病 减少人口接触这些 这些因素可能会导致公共卫生负担大幅减少， AD. 研究人员指出，基于人群的双胞胎设计仍然是 理想的方法来进行这类调查，但这样的成本 研究是一个问题。 他们进一步指出，改变目前的 工作计划导致预算减少19.2%，与 事先申请。