APOE and dementia – resequencing and genotyping in 105,597 individuals

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APOE and dementia – resequencing and genotyping in 105,597 individuals. / Rasmussen, Katrine L.; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.; Frikke-Schmidt, Ruth.

In: Alzheimer's and Dementia, Vol. 16, No. 12, 2020, p. 1624-1637.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rasmussen, KL, Tybjærg-Hansen, A, Nordestgaard, BG & Frikke-Schmidt, R 2020, 'APOE and dementia – resequencing and genotyping in 105,597 individuals', Alzheimer's and Dementia, vol. 16, no. 12, pp. 1624-1637. https://doi.org/10.1002/alz.12165

APA

Rasmussen, K. L., Tybjærg-Hansen, A., Nordestgaard, B. G., & Frikke-Schmidt, R. (2020). APOE and dementia – resequencing and genotyping in 105,597 individuals. Alzheimer's and Dementia, 16(12), 1624-1637. https://doi.org/10.1002/alz.12165

Vancouver

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. APOE and dementia – resequencing and genotyping in 105,597 individuals. Alzheimer's and Dementia. 2020;16(12):1624-1637. https://doi.org/10.1002/alz.12165

Author

Rasmussen, Katrine L. ; Tybjærg-Hansen, Anne ; Nordestgaard, Børge G. ; Frikke-Schmidt, Ruth. / APOE and dementia – resequencing and genotyping in 105,597 individuals. In: Alzheimer's and Dementia. 2020 ; Vol. 16, No. 12. pp. 1624-1637.

Bibtex

@article{f894bb00f79b4051bd7bfee219e7d088,
title = "APOE and dementia – resequencing and genotyping in 105,597 individuals",
abstract = "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.",
keywords = "Alzheimer's disease, APOE, apolipoprotein E, dementia, genetics, rare variation",
author = "Rasmussen, {Katrine L.} and Anne Tybj{\ae}rg-Hansen and Nordestgaard, {B{\o}rge G.} and Ruth Frikke-Schmidt",
year = "2020",
doi = "10.1002/alz.12165",
language = "English",
volume = "16",
pages = "1624--1637",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "Elsevier",
number = "12",

}

RIS

TY - JOUR

T1 - APOE and dementia – resequencing and genotyping in 105,597 individuals

AU - Rasmussen, Katrine L.

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G.

AU - Frikke-Schmidt, Ruth

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - APOE

KW - apolipoprotein E

KW - dementia

KW - genetics

KW - rare variation

U2 - 10.1002/alz.12165

DO - 10.1002/alz.12165

M3 - Journal article

C2 - 32808727

AN - SCOPUS:85089524375

VL - 16

SP - 1624

EP - 1637

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

SN - 1552-5260

IS - 12

ER -

ID: 253078036