| Title: |
Risk score roulette: A cautionary tale of polygenic risk score reliability |
| Authors: |
Xue, Diane; Blue, Elizabeth E; Wood, Alexis C; Rotter, Jerome I; Fohner, Alison E |
| Contributors: |
National Institute on Aging |
| Source: |
Journal of Alzheimer’s Disease ; volume 108, issue 1, page 65-70 ; ISSN 1387-2877 1875-8908 |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2025 |
| Description: |
Genetic risk prediction for Alzheimer's disease (AD) has high potential impact, yet few studies have assessed the reliability of various polygenic risk score (PRS) methods at the individual level. Here, we evaluated the reliability of AD PRS estimates among 6338 participants from the Multi-Ethnic Study of Atherosclerosis. We compared four PRS models that have been previously associated with dementia risk. Despite similar population-level performance metrics, inter-model reliability of individual-level risk assessment was low, even among individuals classified in the top and bottom deciles. These findings raise serious concerns about the downstream application of PRS for guiding interventions for AD. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1177/13872877251375098 |
| Availability: |
https://doi.org/10.1177/13872877251375098; https://journals.sagepub.com/doi/pdf/10.1177/13872877251375098; https://journals.sagepub.com/doi/full-xml/10.1177/13872877251375098 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ ; https://journals.sagepub.com/page/policies/text-and-data-mining-license |
| Accession Number: |
edsbas.C4FDEB61 |
| Database: |
BASE |