APOE and dementia – resequencing and genotyping in 105,597 individuals
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- APOE and dementia – resequencing and genotyping in 105,597 individuals
Forlagets udgivne version, 1,21 MB, PDF-dokument
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Alzheimer's and Dementia |
Vol/bind | 16 |
Udgave nummer | 12 |
Sider (fra-til) | 1624-1637 |
Antal sider | 14 |
ISSN | 1552-5260 |
DOI | |
Status | Udgivet - 2020 |
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 253078036