Abstract

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms. Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2; = .003). The difference in the same PRS between ε3/ε3 extremes was not as significant (OR 3.13; CI 0.98-9.92; = .053) despite similar numbers and power. There was no statistical difference in an educational attainment PRS between these age extreme case-controls. Discussion: A PRS for AD contributes to modified cognitive expression of the ε4/ε4 genotype at phenotypic extremes of risk.

RAS ID

36631

Document Type

Journal Article

Date of Publication

1-1-2021

Funding Information

Funding information available in the Acknowledgements section of the PDF

School

School of Medical and Health Sciences / Centre for Precision Health

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Publisher

Wiley

Comments

Huq, A. J., Fulton‐Howard, B., Riaz, M., Laws, S., Sebra, R., Ryan, J., ... & Lacaze, P. (2021). Polygenic score modifies risk for Alzheimer's disease in APOE ε4 homozygotes at phenotypic extremes. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 13(1), e12226. https://doi.org/10.1002/dad2.12226

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Neurosciences Commons

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Link to publisher version (DOI)

10.1002/dad2.12226