Cumulative Genetic Risk and APOE e4 Are Independently Associated with Dementia Status in a Multiethnic, Population-Based Cohort

Details

• Personal Author:
  Bakulski KM ; Benke KS ; Faul JD ; Heeringa SG ; Kardia SLR ; Langa KM ; Manly JJ ; Mitchell CM ; Smith JA ; Vadari HS ; Ware EB
• Description:
  Objective: Alzheimer disease (AD) is a common and costly neurodegenerative disorder. A large proportion of AD risk is heritable, and many genetic risk factors have been identified. The objective of this study was to test the hypothesis that cumulative genetic risk of known AD markers contributed to odds of dementia in a population-based sample. Methods: In the US population-based Health and Retirement Study (waves 1995-2014), we evaluated the role of cumulative genetic risk of AD, with and without the APOE e4 alleles, on dementia status (dementia, cognitive impairment without dementia, borderline cognitive impairment without dementia, and cognitively normal). We used logistic regression, accounting for demographic covariates and genetic principal components, and analyses were stratified by European and African genetic ancestry. Results: In the European ancestry sample (n = 8,399), both AD polygenic score excluding the APOE genetic region (odds ratio [OR] = 1.10; 95% confidence interval [CI]: 1.00-1.20) and the presence of any APOE e4 alleles (OR = 2.42; 95% CI: 1.99-2.95) were associated with the odds of dementia relative to normal cognition in a mutually adjusted model. In the African ancestry sample (n = 1,605), the presence of any APOE e4 alleles was associated with 1.77 (95% CI: 1.20-2.61) times higher odds of dementia, whereas the AD polygenic score excluding the APOE genetic region was not significantly associated with the odds of dementia relative to normal cognition 1.06 (95% CI: 0.97-1.30). Conclusions: Cumulative genetic risk of AD and APOE e4 are both independent predictors of dementia in European ancestry. This study provides important insight into the polygenic nature of dementia and demonstrates the utility of polygenic scores in dementia research. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Epidemiology Genetics Nervous System Occupational Health Safety
• Keywords:
  Cognitive Function Cohort Studies Genetic Factors Population Based
• ISSN:
  2376-7839
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Michigan ; New York ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  7
• Issue:
  2
• NIOSHTIC Number:
  nn:20070658
• Citation:
  Neurol Genet 2021 Apr; 7(2):e576
• Email:
  bakulski@umich.edu
• Federal Fiscal Year:
  2021
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Neurology: Genetics
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5af70088035cdd139263d39680b3a6b76663d40b45b52aafcf96337a55f44ac3c2e0cb529281050eb9f0f2094a56f5410efa7c62a347a113e6ebe38ddc41ed2d
• Download URL:
  https://stacks.cdc.gov/view/cdc/208835/cdc_208835_DS1.pdf
• File Type:
  [PDF - 217.42 KB ]