Authors/Creators
Aamira J. Huq
Brian Fulton-Howard
Moeen Riaz
Simon Laws, Edith Cowan UniversityFollow
Robert Sebra
Joanne Ryan
Alzheimer’s Disease Genetics Consortium
Alan E. Renton
Alison M. Goate
Colin L. Masters
Elsdon Storey
Raj C. Shah
Anne Murray
John McNeil
Ingrid Winship
Paul A. Jones
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
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