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Polygenic Risk Scores for Incident Dementia in the Multi‐Ethnic Study of Atherosclerosis
Diane Xue, Elizabeth Blue, Tamar Sofer, Timothy M. Hughes, Jerome I. Rotter, Wendy S. Post, Alison E. Fohner. Genetic Epidemiology, 2026-06-23
Topic: Risk, prevention and care in population studies
ABSTRACT Over 75 Alzheimer's disease (AD) and dementia‐associated variants have been identified through genome‐wide association studies, but the utility of polygenic risk scores (PRS) for predicting AD and dementia in diverse and admixed populations remains unclear. We compared how PRS approaches differing in p ‐value thresholds, variant weights, and source ancestry perform in predicting dementia in 6338 African American, Chinese, Hispanic, and White individuals from the Multi‐Ethnic Study of Atherosclerosis. We tested clumping and thresholding (C+T) methods with varying parameters against Bayesian approaches (PRS‐CS, PRS‐CSx). We compared the ability of each method to predict incident dementia in all participants and in groups stratified by self‐reported race/ethnicity. We additionally analyzed performance across groups stratified by estimated proportion of non‐Finnish European (NFE)‐like ancestry. Including more variants does not improve performance. We found comparable associations between dementia and PRS when comparing a C+T method with only 15 SNPs and PRS derived from Bayesian models that include > 800,000 SNPs (HR 5e‐08 = 1.18, 95% CI: 1.08–1.28; HR CSx = 1.17, 95% CI: 1.07−1.27). The p < 5e‐08 C+T method was more strongly associated with incident dementia in populations genetically dissimilar from the source data (HR lowNFE _ 5e‐08 = 1.27, 95% CI: 1.08−1.50; HR lowNFE _ CSx = 1.12, 95% CI: 0.94−1.33). More selective PRS models using genome‐wide significant SNPs may be preferable for dementia prediction in diverse populations.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Xue, D., Blue, E., Sofer, T., Hughes, T. M., Rotter, J. I., Post, W. S., et al. (2026). Polygenic Risk Scores for Incident Dementia in the Multi‐Ethnic Study of Atherosclerosis. Genetic Epidemiology. https://doi.org/10.1002/gepi.70046
Vancouver
Xue D, Blue E, Sofer T, Hughes TM, Rotter JI, Post WS, et al. Polygenic Risk Scores for Incident Dementia in the Multi‐Ethnic Study of Atherosclerosis. Genetic Epidemiology. 2026. doi:10.1002/gepi.70046. PMID: 40093241.
BibTeX
@article{xue2026-40093241,
author = {Xue, Diane and Blue, Elizabeth and Sofer, Tamar and Hughes, Timothy M. and Rotter, Jerome I. and Post, Wendy S. and Fohner, Alison E.},
title = {{Polygenic Risk Scores for Incident Dementia in the Multi‐Ethnic Study of Atherosclerosis}},
journal = {Genetic Epidemiology},
year = {2026},
doi = {10.1002/gepi.70046},
pmid = {40093241},
url = {https://doi.org/10.1002/gepi.70046}
}
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Key findings
- We found comparable associations between dementia and PRS when comparing a C+T method with only 15 SNPs and PRS derived from Bayesian models that include > 800,000 SNPs (HR 5e‐08 = 1.18, 95% CI: 1.08–1.28; HR CSx = 1.17, 95% CI: 1.07−1.27).
- The p < 5e‐08 C+T method was more strongly associated with incident dementia in populations genetically dissimilar from the source data (HR lowNFE _ 5e‐08 = 1.27, 95% CI: 1.08−1.50; HR lowNFE _ CSx = 1.12, 95% CI: 0.94−1.33).
- More selective PRS models using genome‐wide significant SNPs may be preferable for dementia prediction in diverse populations.
Why it matters
This study found that a polygenic risk score using only 15 genetic variants performed comparably to scores using over 800,000 variants in predicting incident dementia across diverse ethnic groups. It suggests that simpler genetic risk scores may be useful, but it does not test a treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Genetic Epidemiology) |
| Journal's citation record | 1 / 4 | Genetic Epidemiology: journal h-index 132 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 9.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Alison E. Fohner: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40093241) |
| Free to read | 2 / 2 | Free to read |
| Total | 44 / 100 | — |
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