De Marco, M. orcid.org/0000-0002-9240-8067, Manca, R. orcid.org/0000-0003-1715-6442, Kirby, J. orcid.org/0000-0002-7468-5917 et al. (5 more authors) (2020) The association between polygenic hazard and markers of Alzheimer’s disease following stratification for APOE genotype. Current Alzheimer Research, 17 (7). pp. 667-679. ISSN 1567-2050
Abstract
Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles.
Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers.
Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps.
Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants.
Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Bentham Science Publishers. This is an author-produced version of a paper subsequently published in Current Alzheimer Research. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Mild cognitive impairment; apolipoprotein; memory; executive function; polygenic traits; amyloid |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Jan 2021 10:35 |
Last Modified: | 16 Nov 2021 01:38 |
Status: | Published |
Publisher: | Bentham Science Publishers Ltd. |
Refereed: | Yes |
Identification Number: | 10.2174/1567205017666201006161800 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:170128 |