| Title: |
Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals |
| Authors: |
Yu, Chenglong; Ryan, Joanne; Orchard, Suzanne G.; Robb, Catherine; Woods, Robyn L.; Wolfe, Rory; Renton, Alan E.; Goate, Alison M.; Brodtmann, Amy; Shah, Raj C.; Chong, Trevor T.‐J.; Sheets, Kerry; Kyndt, Christopher; Sood, Ajay; Storey, Elsdon; Murray, Anne M.; McNeil, John J.; Lacaze, Paul |
| Contributors: |
National Institutes of Health |
| Source: |
Alzheimer's & Dementia ; volume 19, issue 12, page 5333-5342 ; ISSN 1552-5260 1552-5279 |
| Publisher Information: |
Wiley |
| Publication Year: |
2023 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
INTRODUCTION Recent genome‐wide association studies identified new dementia‐associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. METHODS We used Cox models and area under the curve (AUC) to validate new PRSs (PRS‐83SNP, PRS‐SBayesR, and PRS‐CS) compared with an older PRS‐23SNP in 12,031 initially‐healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) criteria. RESULTS PRS‐83SNP, PRS‐SBayesR, and PRS‐CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [ APOE ] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23–1.47), 1.37 (1.25–1.50), and 1.42 (1.30–1.56), respectively. The AUC of a model containing conventional/non‐genetic factors and APOE was 74.7%. This was improved to 75.7% ( p = 0.007), 76% ( p = 0.004), and 76.1% ( p = 0.003) with addition of PRS‐83SNP, PRS‐SBayesR, and PRS‐CS, respectively. The PRS‐23SNP did not improve AUC (74.7%, p = 0.95). CONCLUSION New PRSs for dementia significantly improve risk‐prediction performance, but still account for less risk than APOE genotype overall. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/alz.13113 |
| Availability: |
https://doi.org/10.1002/alz.13113 |
| Rights: |
http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.F85E49CF |
| Database: |
BASE |