APOE and dementia – resequencing and genotyping in 105,597 individuals
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- APOE and dementia – resequencing and genotyping in 105,597 individuals
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Introduction: The mechanism behind the strong association between the ɛ2/ɛ3/ɛ4 apolipoprotein E gene (APOE) polymorphism and Alzheimer's disease is not well-characterized. Because low plasma levels of apoE associate with risk of dementia, genetic variants altering apoE levels in general may also associate with dementia. Methods: The APOE gene was sequenced in 10,369 individuals, and nine amino acid–changing variants with frequencies ≥2/10,000 were further genotyped in 95,228 individuals. Plasma apoE levels were measured directly. Results: Risk of all dementia and Alzheimer's disease (AD) increased with decreasing genetically determined apoE levels (P = 5 × 10−4 and P = 1 × 10−4 after APOE ɛ2/ɛ3/ɛ4 adjustment). Hazard ratios (95% confidence intervals) for all dementia and AD were 2.76 (1.39 to 5.47) and 4.92 (2.36 to 10.29) for the group with the genetically lowest apoE versus ɛ33. Discussion: We found that genetically low apoE levels increase and genetically high levels decrease risk, beyond ɛ2/ɛ3/ɛ4. This underscores that dementia risk more likely relates to variants affecting levels of apoE.
Original language | English |
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Journal | Alzheimer's and Dementia |
Volume | 16 |
Issue number | 12 |
Pages (from-to) | 1624-1637 |
Number of pages | 14 |
ISSN | 1552-5260 |
DOIs | |
Publication status | Published - 2020 |
- Alzheimer's disease, APOE, apolipoprotein E, dementia, genetics, rare variation
Research areas
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