Year: 2019
Type: article
Study design: Observational Study
Abstract: Alzheimer's disease (AD) is a prevalent and costly neurodegenerative disorder. A large proportion of risk is heritable and many genetic risk factors for AD have been identified. The cumulative genetic risk of these known markers has not been benchmarked in a population-based sample. In the nationally representative, population-based Health and Retirement Study (HRS), we evaluated the role of cumulative genetic risk for AD, with and without APOE status, on dementia status (dementia, cognitively impaired non-demented, cognitively normal) using proportional odds models. Analyses were stratified by European (EA) and African (AA) genetic ancestry participants (nEA=8,297, nAA=1,458, waves 1992-2014). In the European ancestry sample, a one standard deviation unit increase in polygenic score for AD was associated with 1.13 (95% confidence interval: 1.04, 1.23) times higher odds of dementia, relative to normal cognition. The presence of APOE ε4 was independently associated with 2.19 (95% confidence interval: 1.82, 2.65) times higher odds of having dementia. In the African ancestry sample, a one standard deviation unit increase in polygenic score for AD was associated with 1.21 (95% confidence interval: 0.99, 1.46) times higher odds of dementia. Carrying APOE ε4 was associated with 1.15 (95% confidence interval: 1.14, 1.77) times higher odds of dementia. Cumulative genetic risk for AD and APOE ε4 are both independent predictors of AD and the magnitudes of association vary by genetic ancestry. We provide important insight into the polygenic nature of dementia and demonstrate the utility of polygenic scores in AD research
Source: Alzheimer s & Dementia
Institutions: University of Michigan, Johns Hopkins University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980856496