Luckett, ES;
Abakkouy, Y;
Lorenzini, L;
Collij, LE;
Garcia, DV;
Visser, PJ;
Den Braber, A;
... AMYPAD Consortium; + view all
(2025)
Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium.
Alzheimer's & Dementia
, 21
(9)
, Article e70376. 10.1002/alz.70376.
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Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium.pdf - Published Version Download (2MB) | Preview |
Abstract
INTRODUCTION: We sought to harmonize genotype data from the predementia AMYPAD (Amyloid Imaging to Prevent Alzheimer's Disease) Consortium, compute polygenic risk scores (PRS), and determine their association with global amyloid deposition. // METHODS: Genetic data from five AMYPAD parent cohorts were harmonized, and PRS were computed for Alzheimer's disease (AD) susceptibility, cerebrospinal fluid (CSF) amyloid beta (Aβ)42, and CSF phosphorylated tau181. Cross-sectional amyloid (Centiloid [CL]) burden was available for all participants, and regression models determined if PRS were associated with CL burden. // RESULTS: After harmonization, data for 867 participants showed that high CL burden was most strongly predicted by CSF Aβ42 PRS compared to traditional AD susceptibility PRS. // DISCUSSION: This work emphasizes the importance of data harmonization and pooling of cohorts for large-powered studies. Findings suggest a genetic predisposition to amyloid pathology that may predispose individuals early in the AD continuum. This validates the potential use of PRS in clinical (trial) settings as a non-invasive tool to assess AD risk.
| Type: | Article |
|---|---|
| Title: | Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.70376 |
| Publisher version: | https://doi.org/10.1002/alz.70376 |
| Language: | English |
| Additional information: | Copyright © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, https://creativecommons.org/licenses/by-nc-nd/4.0/, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | Alzheimer’s disease, amyloid, Amyloid Imaging to Prevent Alzheimer’s Disease, genotype data harmonization, polygenic risk scores, predementia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215071 |
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