Topic: Amyloid, tau and blood-test diagnosis
Regardless of method or adjustment, the resulting heritability estimates were highly variable across populations. Using S.A.G.E. adjusted for age and sex (model 1), estimates were highest for the Dutch isolates (78.3%) followed by non-Hispanic Blacks (39.1%), Dominicans (31.7%), and non-Hispanic Whites (29.1%). The inclusion of APOE ε4 carrier status (model 2) reduced heritability estimates by an average of 4.9%, with the largest reductions observed in non-Hispanic Blacks (6.7%) and non-Hispanic Whites (6.2%). Cohort adjustment (models 3) primarily affected the estimates for the non-Hispanic Whites (2.4% decrease), reflecting their greater contributions to cohort diversity. The Puerto Rican dataset failed to converge in all models due to small sample size. In general, narrow sense heritability estimates were almost always higher (45.4% - 80.0%) using SOLAR compared with S.A.G.E. (20.4% - 81.9%), reflecting differences in modeling and handling of missing data, while relative patterns and trends remained consistent regardless of magnitude. While family-based estimates complement previous twin-based and genome-wide studies, the wide range of narrow sense heritability estimated across populations reflects substantial variability in population-specific and unmeasured extrinsic factors, such as lifestyle and behaviors, environmental exposures, and social determinants of health. Work supported by AG074865 and AG072547 is ongoing to estimate SNP-based heritability in overlapping participants for direct comparisons with family-based heritability.
Key findings
- Regardless of method or adjustment, the resulting heritability estimates were highly variable across populations.
- Using S.A.G.E. adjusted for age and sex (model 1), estimates were highest for the Dutch isolates (78.3%) followed by non-Hispanic Blacks (39.1%), Dominicans (31.7%), and non-Hispanic Whites (29.1%).
- The inclusion of APOE ε4 carrier status (model 2) reduced heritability estimates by an average of 4.9%, with the largest reductions observed in non-Hispanic Blacks (6.7%) and non-Hispanic Whites (6.2%).
- Cohort adjustment (models 3) primarily affected the estimates for the non-Hispanic Whites (2.4% decrease), reflecting their greater contributions to cohort diversity.
- The Puerto Rican dataset failed to converge in all models due to small sample size.
Why it matters
This study found that estimates of how much Alzheimer disease is inherited varied widely across different populations, and including APOE ε4 status reduced those estimates. It highlights that population-specific and unmeasured factors such as lifestyle and environment contribute to these differences, but it does not test any treatment or prevention.
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Study details
- Participants7,024
- Effect size78.3%; 39.1%; 31.7%
- Evidence strengthModerate
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 7,024 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Scott M. Williams: h-index 73 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41436227) |
| Free to read | 2 / 2 | Free to read |
| Total | 45 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70855_102132
- PubMed: 41436227
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Liu, S., Bush, W. S., Kunkle, B. W., Byrd, G. S., Reitz, C., Tosto, G., et al. (2025). Dissecting Alzheimer Disease Heritability Across Multiple Populations. Alzheimer s & Dementia. https://doi.org/10.1002/alz70855_102132
Vancouver
Liu S, Bush WS, Kunkle BW, Byrd GS, Reitz C, Tosto G, et al. Dissecting Alzheimer Disease Heritability Across Multiple Populations. Alzheimer s & Dementia. 2025. doi:10.1002/alz70855_102132. PMID: 41436227.
BibTeX
@article{liu2025-41436227,
author = {Liu, Shiying and Bush, William S. and Kunkle, Brian W. and Byrd, Goldie S. and Reitz, Christiane and Tosto, Giuseppe and Vance, Jeffery M. and Pericak‐Vance, Margaret and others},
title = {{Dissecting Alzheimer Disease Heritability Across Multiple Populations}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70855_102132},
pmid = {41436227},
url = {https://doi.org/10.1002/alz70855_102132}
}
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