Open AccessPolygenic score modifies risk for Alzheimer's disease in APOE ε4 homozygotes at phenotypic extremes
Author(s) -
Huq Aamira J.,
FultonHoward 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
Publication year - 2021
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12226
Subject(s) - apolipoprotein e , odds ratio , confidence interval , medicine , genotype , disease , alzheimer's disease , psychology , oncology , demography , biology , genetics , gene , sociology
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.