Topic: Amyloid, tau and blood-test diagnosis
Introduction Alzheimer's disease (AD) is the most prevalent form of dementia. While many AD-associated genetic determinants have been identified, few studies have analyzed individuals of non-European ancestry. Methods We conducted a multi-ancestry genome-wide association study (GWAS) of clinically diagnosed AD and AD-by-proxy using whole genome sequencing data from the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS), National Institute of Mental Health, UK Biobank (UKB), and All of Us (AoU) consisting of 49,149 cases (12,074 clinically diagnosed and 37,075 AD-by-proxy) and 383,225 controls. Nearly half of NIAGADS and AoU participants were of non-European ancestry. Results For clinically diagnosed AD, we identified 14 new loci-five common (FBN2/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1, and SLC35G3/AC022916.1). Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1 and CEBPA/AC008738.6), also nominally significant in NIAGADS. Discussion In summary, we provide evidence for 16 novel AD loci and advocate for more studies using whole genome sequencing-based GWAS of diverse cohorts. Highlights We used whole-genome sequencing data from large and diverse cohorts. We found novel genome-wide association study findings based on whole-genome data. We performed a multiancestry meta-analysis and incorporated results from underrepresented groups.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Willett, J. D. S., Waqas, M., Choi, Y., Ngai, T., Mullin, K., Tanzi, R. E., et al. (2025). Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses. Alzheimer's & Dementia. https://doi.org/10.1002/alz.14592
Vancouver
Willett JDS, Waqas M, Choi Y, Ngai T, Mullin K, Tanzi RE, et al. Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses. Alzheimer's & Dementia. 2025. doi:10.1002/alz.14592. PMID: 39998322.
BibTeX
@article{willett2025-39998322,
author = {Willett, J. D. S. and Waqas, M. and Choi, Y. and Ngai, T. and Mullin, K. and Tanzi, R. E. and Prokopenko, D.},
title = {{Identification of 16 novel Alzheimer's disease loci using multi-ancestry meta-analyses}},
journal = {Alzheimer's \& Dementia},
year = {2025},
doi = {10.1002/alz.14592},
pmid = {39998322},
url = {https://doi.org/10.1002/alz.14592}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Results For clinically diagnosed AD, we identified 14 new loci-five common (FBN2/SCL27A6, AC090115.1, DYM, KCNG1/AL121785.1, TIAM1) and nine rare (VWA5B1, RNU6-755P/LMX1A, MOB1A, MORC1-AS1, LINC00989, PDE4D, RNU2-49P/CDO1, NEO1, and SLC35G3/AC022916.1).
- Meta-analysis of UKB and AoU AD-by-proxy cases yielded two new rare loci (RPL23/LASP1 and CEBPA/AC008738.6), also nominally significant in NIAGADS.
- We found novel genome-wide association study findings based on whole-genome data.
- We performed a multiancestry meta-analysis and incorporated results from underrepresented groups.
Why it matters
This multi-ancestry genome-wide association study identified 16 new genetic locations linked to Alzheimer disease, using data that included many participants of non-European ancestry. These findings add to understanding of the disease's genetics and argue for more studies in diverse populations, but they do not yet provide a treatment or cure.
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Study details
- Study designmeta-analysis
- Participants432,374
- Evidence strengthModerate
Limitations
AD-by-proxy phenotypes in UK Biobank and All of Us correlate with clinical AD mainly in homogeneous European-ancestry biobanks; 59% of genome-wide significant variants in All of Us were indels or multi-allelic variants that may be sequencing artefacts or confounded, and the authors stress validation in clinically defined independent datasets.
How this study scored 66/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported 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 | 12 / 12 | A meta-analysis pooling many studies |
| 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 | 4 / 4 | 432,374 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | A review of other studies — randomization is not credited here |
| Times cited | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.4× 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 | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Dmitry Prokopenko: h-index 27 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39998322) |
| 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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