Dataset Information

Polygenic score modifies risk for Alzheimer's disease in APOE ε4 homozygotes at phenotypic extremes.

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.

SUBMITTER: Huq AJ

PROVIDER: S-EPMC8339682 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Polygenic score modifies risk for Alzheimer's disease in <i>APOE</i> ε4 homozygotes at phenotypic extremes.

Huq Aamira J AJ Fulton-Howard Brian B Riaz Moeen M Laws Simon S Sebra Robert R Ryan Joanne J Renton Alan E AE Goate Alison M AM Masters Colin L CL Storey Elsdon E Shah Raj C RC Murray Anne A McNeil John J Winship Ingrid I James Paul A PA Lacaze Paul P

Alzheimer's & dementia (Amsterdam, Netherlands) 20210805 1

<h4>Introduction</h4>Diversity in cognition among apolipoprotein E (<i>APOE</i>) ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms.<h4>Methods</h4>We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy <i>APOE</i> ε4 homozygotes aged ≥75 years (n = 213) and early-onset <i>APOE</i> ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity.<h4>Results</h4>The PRS for AD was significa ...[more]

PMID: 34386572

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