Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals
Yu C, Ryan J, Orchard SG, Robb C, Woods RL, Wolfe R, Renton AE, Goate AM, Brodtmann A, Shah RC, Chong TT, Sheets K, et al.. Alzheimer's & Dementia, 2023-05-12
Topic: Risk, prevention and care in population studies
Plain-language summary
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.
What this study adds
Evidence grade: Moderate
This is a follow-up (cohort) study of 12,031 participants. New polygenic risk scores were associated with incident dementia and slightly improved risk prediction beyond conventional factors and APOE, while an older score did not. Reported effect size: HR 1.35-1.42 per SD of polygenic risk score for incident dementia, independent of APOE ε4.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Yu, C., Ryan, J., Orchard, S. G., Robb, C., Woods, R. L., Wolfe, R., et al. (2023). Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals. Alzheimer's & Dementia. https://doi.org/10.1002/alz.13113
Vancouver
Yu C, Ryan J, Orchard SG, Robb C, Woods RL, Wolfe R, et al. Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals. Alzheimer's & Dementia. 2023. doi:10.1002/alz.13113. PMID: 37177856.
BibTeX
@article{yu2023-37177856,
author = {Yu, C. and Ryan, J. and Orchard, S. G. and Robb, C. and Woods, R. L. and Wolfe, R. and Renton, A. E. and Goate, A. M. and Brodtmann, A. and Shah, R. C. and Chong, T. T. and Sheets, K. and others},
title = {{Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals}},
journal = {Alzheimer's \& Dementia},
year = {2023},
doi = {10.1002/alz.13113},
pmid = {37177856},
url = {https://doi.org/10.1002/alz.13113}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- 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.
- 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.
- Conclusion New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.
Why it matters
New polygenic risk scores were associated with incident dementia and slightly improved risk prediction beyond conventional factors and APOE, while an older score did not. However, the new scores still accounted for less risk than APOE genotype overall.
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Study details
- Study designcohort
- Participants12,031
- Effect sizeHR 1.35-1.42 per SD of polygenic risk score for incident dementia, independent of APOE ε4
- Evidence strengthModerate
Limitations
European-ancestry participants only; ASPREE has a healthy-survivor bias with lower dementia incidence than the general population, which may underestimate PRS effects; dementia adjudication captured all-cause dementia without clinical subtyping.
How this study scored 66/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 65 of the 98 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 4 / 4 | 12,031 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 24 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.8 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Paul A Lacaze: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Minnesota: institution h-index 1,568 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37177856) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 65 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 65 of the 98 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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