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.
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.
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