Harmonizing genotype array data to understand genetic risk for brain amyloid burden in the AMYPAD PNHS Consortium
We developed a robust harmonization pipeline for multi-cohort genotype array data. Cerebrospinal fluid amyloid beta (Aβ)-specific polygenic risk scores (PRS) more strongly predicted global Aβ positron emission tomography burden than other PRS. Results suggest a strong genetic predisposition to early Aβ pathology. This work highlights the need for robust data harmonization and data pooling. This work also validates the potential use of PRS as a non-invasive tool to assess Alzheimer's disease risk.
Authors
- Emma S. Luckett (ORCID: https://orcid.org/0000-0003-1777-4742)
- David Vállez García (ORCID: https://orcid.org/0000-0003-3308-3167)
- Luigi Lorenzini (ORCID: https://orcid.org/0000-0002-9756-881X)
- Pieter Jelle Visser (ORCID: https://orcid.org/0000-0001-8008-9727)
- Craig Ritchie (ORCID: https://orcid.org/0000-0002-6202-6906)
- Anouk den Braber (ORCID: https://orcid.org/0000-0002-3377-2627)
- Merçé Boada (ORCID: https://orcid.org/0000-0003-2617-3009)
- Yasmina Abakkouy (ORCID: https://orcid.org/0000-0002-6601-4048)
- Frederik Barkhof (ORCID: https://orcid.org/0000-0003-3543-3706)
- Juan Domingo Gispert (ORCID: https://orcid.org/0000-0002-6155-0642)
- Rik R. Vandenberghe (ORCID: https://orcid.org/0000-0001-6237-2502)
- Patricia Genius (ORCID: https://orcid.org/0000-0003-1836-5123)
- Natàlia Vilor‐Tejedor (ORCID: https://orcid.org/0000-0003-4935-6721)
- Isabelle Cleynen (ORCID: https://orcid.org/0000-0003-0857-7683)
- Lyduine E. Collij
Institutions
- Allen Institute for Brain Science (US)
- Radboud University Nijmegen (NL)
- University of St Andrews (GB)
- Universitat Pompeu Fabra (ES)
- Lund University (SE)
- Instituto de Salud Carlos III (ES)
- Radboud University Medical Center (NL)
- Karolinska Institutet (SE)
- Universitat Internacional de Catalunya (ES)
- Maastricht University (NL)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Center for Human Genetics (US)
- Pasqual Maragall Foundation (ES)
- Amsterdam Neuroscience (NL)
- Hospital Del Mar (ES)
- Barcelona Institute of Science and Technology (ES)
- Municipal Institute for Medical Research (ES)
- Centre for Genomic Regulation (ES)
- National Hospital for Neurology and Neurosurgery (GB)
- Amsterdam University Medical Centers (NL)
- Hospital del Mar Research Institute (ES)
- Institute of Neurobiology (BG)
- University College London (GB)
- Vrije Universiteit Amsterdam (NL)
- KU Leuven (BE)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1002/alz.70376
- Citations
- 1
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 1.47
Funders
- Eli Lilly and Company
- Agentschap Innoveren en Ondernemen
- European Federation of Pharmaceutical Industries and Associations
- National Institute for Health and Care Research
- European Commission
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- University College London Hospitals NHS Foundation Trust
- Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona
- Agencia Estatal de Investigación