Polygenic score modifies risk for Alzheimer's disease in APOE ε4 homozygotes at phenotypic extremes. Issue 1 (5th August 2021)

• Record Type: Journal Article
• Authors: Huq, Aamira J.; Fulton‐Howard, Brian; Riaz, Moeen; Laws, Simon; Sebra, Robert; Ryan, Joanne; Renton, Alan E.; Goate, Alison M.; Masters, Colin L.; Storey, Elsdon; Shah, Raj C.; Murray, Anne; McNeil, John; Winship, Ingrid; James, Paul A.; Lacaze, Paul
• Is Part Of: Alzheimer's & dementia. Volume 13:Issue 1(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-05
• Subjects: Alzheimer's disease -- Alzheimer's disease dementia -- apolipoprotein E -- dementia resilience -- genetic modifiers -- polygenic risk score; Alzheimer's disease -- Periodicals; Alzheimer's disease -- Diagnosis -- Periodicals; Dementia -- Periodicals; Dementia -- Diagnosis -- Periodicals; 616.831
• DOI: 10.1002/dad2.12226
• Languages: English
• ISSNs: 2352-8729

Abstract

Abstract: Introduction: Diversity in cognition among apolipoprotein E ( APOE ) 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 APOE ε4 homozygotes aged ≥75 years (n = 213) and early‐onset APOE ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in APOE ε4 homozygote AD cases compared to older cognitively healthy APOE ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0–35.2; P = .003). The difference in the same PRS between APOE ε3/ε3 extremes was not as significant (OR 3.13; CI 0.98–9.92; P = .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 APOE ε4/ε4 genotype at phenotypic extremes of risk.