Genetic risk for Alzheimer's disease is distinct from genetic risk for amyloid deposition

Leonenko, Ganna ORCID: https://orcid.org/0000-0001-8025-661X, Shoai, Maryam, Bellou, Eftychia, Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Hardy, John, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483 and the Alzheimer's Disease Neuroimaging Initiative 2019. Genetic risk for Alzheimer's disease is distinct from genetic risk for amyloid deposition. Annals of Neurology 86 (3) , pp. 427-435. 10.1002/ana.25530

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Abstract

Objectives Alzheimer's disease (AD) is the most common form of dementia and is responsible for a huge and growing health care burden in the developed and developing world. The Polygenic Risk Score (PRS) approach has shown 75%‐84% prediction accuracy of identifying individuals with AD risk. Methods In this study we tested the prediction accuracy of AD, MCI and amyloid deposition risks with PRS, including and excluding APOE genotypes in a large publicly available data set with extensive phenotypic data: the Alzheimer's Disease Neuroimaging Initiative cohort. Among MCI individuals with amyloid positive status we examined PRS prediction accuracy in those who converted to AD. In addition, we divided polygenic risk score by biological pathways and tested them independently for distinguishing between AD, MCI and amyloid deposition. Results We found that AD and MCI are predicted by both APOE genotype and PRS (AUC=0.82% and 68%, respectively). Amyloid deposition is predicted by APOE only (AUC=79%). Further progression to AD of individuals with MCI and amyloid positive status is predicted by PRS over and above APOE (AUC=67%).

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher:	Wiley
ISSN:	0364-5134
Funders:	MRC
Date of First Compliant Deposit:	18 June 2019
Date of Acceptance:	12 June 2019
Last Modified:	26 Jul 2024 16:11
URI:	https://orca.cardiff.ac.uk/id/eprint/123526

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