Genome-Wide Association Study of Cognitive Decline Among Older African Americans

老年非裔美国人认知衰退的全基因组关联研究

• 批准号: 7857527
• 负责人: PHILIP L DE JAGER
• 金额: $ 133.39万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 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/7857527
• 关键词: Address; Admixture; African; African American; Age; Aging; Alzheimer' s Disease; American; Architecture; Biological Markers; Blood Pressure; Chicago; Cholesterol; Chronic Disease; Cohort Studies; Collection; Data; Developed Countries; Developing Countries; Diagnosis; Enrollment; Ethnic group; European; Future; Genetic; Genetic Markers; Glycosylated Hemoglobin; Goals; Health; Healthcare; Impaired cognition; Inpatients; Investigation; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Memory; Minority; Names; Older Population; Outpatients; Parkinsonian Disorders; Phenotype; Physical Function; Population; Principal Investigator; Public Health; Records; Resources; Staging; Stroke; Work; age group; brain volume; cohort; cost; design; disease phenotype; genome wide association study; programs; public health relevance; racial and ethnic; research study

DESCRIPTION (provided by applicant): Large genome-wide association studies (GWASs) of common chronic disease phenotypes among older African Americans are uncommon despite many of these conditions being heavy burdens in this racial/ethnic group. This is especially true of cognitive decline among older people and of Alzheimer's disease (AD), the specific condition most frequently responsible for severe decline in this age group. The public health problems due to these conditions are expected to grow sharply with the continued increase in size of the oldest population age groups in the US and other developed countries. We propose two steps to constructively address this situation at reasonable cost. The first is a large, two-stage GWAS of the phenotype of directly measured cognitive decline among 7,750 older African Americans and Africans enrolled in four collaborating studies: the Chicago Health and Aging Project (CHAP), the Indianapolis-Ibadan Project, the Memory and Aging Project (MAP) and the Minority Aging Research Study (MARS). This work is closely linked to the Alzheimer's Disease Genetic Consortium (ADGC), with whom the GWAS results and all other data will be shared, and will greatly expand its efforts in this racial/ethnic group. The design will permit both designation of an exploratory and independent confirmatory cohorts and a combined analysis of all 6,162 African American subjects, and analyses will efficiently consider the spectrum of admixture among African Americans. The second, coordinated, goal is to establish, as resources for future investigations, GWASs of the four collaborating longitudinal cohort studies: Existing data from these ongoing longitudinal studies assess a number of highly relevant phenotypes among African Americans. In addition to directly measured cognitive decline and AD, the phenotypes assessed in one or more studies include stroke, blood pressure, directly measured physical function, parkinsonian signs, and MRI findings, including white mater hyperintensities and total brain volume. Their value is further enhanced by collection of health care records, both inpatient and outpatient, permitting diagnosis of other phenotypes, and by collection in some studies of several relevant biomarkers included glycosylated hemoglobin and cholesterol. PUBLIC HEALTH RELEVANCE: This proposal will assess the associations of over 900,000 genetic markers with cognitive decline among 7750 older African Americans and Africans. The purpose is to identify genetic factors that are related to this important problem in this under-studied segment of the population.

描述（由申请人提供）：在非洲裔美国人中，大型基因组的慢性疾病表型的大型慢性疾病表型研究（GWASS）并不常见，尽管在这个种族/族裔群体中，其中许多疾病负担沉重。老年人和阿尔茨海默氏病（AD）的认知能力下降尤其如此，这是特定疾病最常 负责该年龄段的严重下降。 随着美国和其他发达国家最古老的人口年龄段的规模持续增加，由于这些条件的公共卫生问题将急剧增长。我们提出了两个步骤，以合理的成本进行建设性地解决这种情况。第一个是在7,750名非洲裔美国人和非洲人中直接测量认知下降的表型的大型，两阶段的GWA，并参加了四项合作研究：芝加哥卫生与老化项目（CHAP），印第安纳波利斯 - 伊比巴达人项目，记忆和衰老项目（MAP）和少数族裔老化研究（MAR研究）（MARS）（MARS）。这项工作与阿尔茨海默氏病遗传联盟（ADGC）紧密相关，GWAS的结果和所有其他数据将被共享，并将大大扩展其在这个种族/族裔群体中的努力。设计将允许 指定探索性和独立的验证性队列的指定以及对所有6,162名非裔美国人受试者的综合分析，以及分析将有效地考虑非裔美国人中混合的范围。 第二个协调的目标是建立作为未来调查的资源，GWASS 在四个合作的纵向队列研究中：这些正在进行的现有数据 纵向研究评估了非裔美国人中许多高度相关的表型。除了直接测量认知能力下降和AD外，在一项或多项研究中评估的表型包括中风，血压，直接测量身体机能，帕金森氏症体征和MRI发现，包括白色母乳高压和总脑体积。通过住院和门诊的医疗记录收集，可以诊断出其他表型，进一步提高了其价值，并在对几种相关生物标志物的一些研究中收集了包括糖基化的血红蛋白和胆固醇。 公共卫生相关性：该提案将评估7750名非裔美国人和非洲人的认知能力下降的900,000多个遗传标记的关联。目的是确定在这个人口不足的人群中与这一重要问题相关的遗传因素。