Genome Wide associate analysis of Alzheimer's Disease

阿尔茨海默病的全基因组关联分析

• 批准号: 7854058
• 负责人: GERARD DAVID SCHELLENBERG
• 金额: $ 344万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854058
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Apolipoprotein E; Blood; Caregivers; Cells; Cognitive; Collection; Communities; Complex; Cost of Illness; DNA; DNA Library; Data; Data Analyses; Data Set; Databases; Deposition; Disease; Disease susceptibility; Elderly; Elements; Emotional; Enrollment; Family; Federal Government; Financial cost; Funding; Genes; Genetic; Genetic Epistasis; Genotype; Goals; Government; Healthcare Systems; Hereditary Disease; Knowledge; Methods; National Institute of Mental Health; Non-Insulin-Dependent Diabetes Mellitus; Odds Ratio; Phenotype; Population; Research; Research Infrastructure; Research Personnel; Resources; Sample Size; Sampling; Susceptibility Gene; Work; base; case control; cohort; cost; density; familial Alzheimer disease; gene discovery; genome wide association study; genome-wide; malignant breast neoplasm; population based; prevent; public health relevance; repository; success

DESCRIPTION (provided by applicant): Genome-wide association (GWA) methods have now been successfully used to detect disease-related susceptibility genes numerous genetically complex disorders. In these studies, a critical element for success is that the sample size be large enough so that there is adequate power to detect genes with small effect sizes at a genome-wide significance level. As an example, type 2 diabetes, susceptibility genes with odds ratios of ~1.3 were detected with cohorts of ~15,000 cases and a comparable number of controls. For AD, preliminary GWA studies utilized samples of 1,000 cases or less have been performed. These studies have the power to detect modest effect loci but not the small effect genes typically found in the analysis of other complex disorders. The primary goals of this application are to: 1) Assemble enough AD cases and comparable elderly normal controls to detect small effect loci; 2) Perform GWA studies using a high- density genotyping platform to detect small effect loci that contribute to AD susceptibility; 3) Analyze a large familial AD collection using the same genotyping platform so that family-based methods can be applied to AD gene discovery; 4) Provide a DNA, phenotype, and genotype resource of well- characterized AD cases, mild cognitive impaired (MCI) subjects, and controls for the genetics community to analyze. The cases, MCI subjects, and controls will be the approximately 16,500 subjects currently being studied by the 29 NIA-funded Alzheimer's Disease Centers (ADC's). Extensive phenotype data as a Uniform Data Set (UDS) for these subjects is in a centralized database (National Alzheimer Coordinating Center or NACC). DNA from these subjects will be deposited in the National Cell Repository for Alzheimer's Disease (NCRAD), an existing repository. A second cohort will be multiplex families with extensive phenotype data and DNA currently available from the NIMH Genetics Initiative repository. This study will make use of the infrastructure of the existing Alzheimer's Disease Genetics Consortium (ADGC) to coordinate that data from multiple GWA studies for subsequent meta and combined analysis of multiple AD GWA studies, and to provide investigators with AD GWA data for subsequent analysis. PUBLIC HEALTH RELEVANCE: Alzheimer's disease affects over 5 million people in the US costing the Federal Government over $100 billion dollars/year. Because our population is aging, in 2050, if the disease remains untreatable, there will be 16 million people in the US with AD costing $1 trillion dollars/year. Presently there are no methods of preventing AD or halting progression. Thus, more fundamental knowledge on disease mechanism is needed.

描述（由申请人提供）：全基因组关联（GWA）方法现已成功地用于检测与疾病相关的易感性基因许多遗传复杂性疾病。在这些研究中，成功​​的关键要素是样本量足够大，因此有足够的能力来检测具有较小效应大小在全基因组显着性水平的基因。例如，2型糖尿病型，比值比为〜1.3的易感基因被检测到约15,000例病例和相当数量的对照组。对于AD，已经进行了1,000例或更少病例的样本的初步GWA研究。这些研究有能力检测适度的效应基因座，但不能检测其他复杂疾病分析中通常发现的小效应基因。该应用的主要目标是：1）组装足够的AD病例和可比的老年正常对照，以检测小效应基因座； 2）使用高密度基因分型平台进行GWA研究，以检测有助于AD敏感性的小效应基因座； 3）使用相同的基因分型平台分析大型家族广告收集，以便可以将基于家庭的方法应用于AD基因发现； 4）提供良好特征的AD病例，轻度认知受损（MCI）受试者的DNA，表型和基因型资源以及遗传学群落的控制。这些病例，MCI受试者和对照组将是29名NIA资助的阿尔茨海默氏病中心（ADC）目前正在研究的大约16,500名受试者。这些受试者的广泛表型数据作为统一的数据集（UDS）在集中式数据库中（国家阿尔茨海默氏症协调中心或NACC）。这些受试者的DNA将存放在现有存储库的阿尔茨海默氏病（NCRAD）的国家细胞存储库中。第二个队列将是具有广泛表型数据和目前可从NIMH Genetics Initiative存储库中获得的大量表型数据和DNA的多重家族。这项研究将利用现有阿尔茨海默氏病遗传联盟（ADGC）的基础设施来协调来自多个GWA研究的数据，以进行多个AD GWA研究，并将研究人员与AD GWA数据一起为后续分析提供研究。 公共卫生相关性：阿尔茨海默氏病影响美国超过500万人，每年耗资超过1000亿美元。由于我们的人口正在衰老，在2050年，如果这种疾病仍然无法治疗，美国将有1600万人每年的广告费用为1万亿美元。目前，没有防止AD或停止进展的方法。因此，需要对疾病机制的更多基本知识。