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Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease
Ali M, Archer DB, Gorijala P, Western D, Timsina J, Fernández MV, Wang TC, Satizabal CL et al.. Acta neuropathologica communications, 2023-04-26
Topic: Amyloid, tau and blood-test diagnosis
Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10 -311 , MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; β = 0.07, SE = 0.01, P = 9.2 × 10 -09 , MAF = 0.32), CR1 (rs6656401/chr1q.32.2; β = 0.1, SE = 0.02, P = 2.4 × 10 -10 , MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; β = 0.16, SE = 0.03, P = 1.1 × 10 -09 , MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, β = 0.79, SE = 0.14, P = 1.4 × 10 -08 , MAF = 0.006, sex-interaction P = 9.8 × 10 -07 ) and chr11p.15.2 (rs192346166, β = 0.94, SE = 0.17, P = 3.7 × 10 -08 , MAF = 0.004, sex-interaction P = 1.3 × 10 -03 ). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ali, M., Archer, D. B., Gorijala, P., Western, D., Timsina, J., Fernández, M. V., et al. (2023). Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease. Acta neuropathologica communications. https://doi.org/10.1186/s40478-023-01563-4
Vancouver
Ali M, Archer DB, Gorijala P, Western D, Timsina J, Fernández MV, et al. Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease. Acta neuropathologica communications. 2023. doi:10.1186/s40478-023-01563-4. PMID: 37101235.
BibTeX
@article{ali2023-37101235,
author = {Ali, M. and Archer, D. B. and Gorijala, P. and Western, D. and Timsina, J. and Fernández, M. V. and Wang, T. C. and Satizabal, C. L. and others},
title = {{Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease}},
journal = {Acta neuropathologica communications},
year = {2023},
doi = {10.1186/s40478-023-01563-4},
pmid = {37101235},
url = {https://doi.org/10.1186/s40478-023-01563-4}
}
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
- We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk.
- We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10 -311 , MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4.
- We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits.
- Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account.
Why it matters
This large multi-ethnic genetic study identified APOE and several other genetic loci associated with brain amyloidosis and Alzheimer's disease risk, including some female-specific signals. It is a genetic association study and does not report any treatment, cure, or prevention of Alzheimer's disease.
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Study details
- Participants13,409
- Evidence strengthLow
Limitations
The abstract doesn't specify how the amyloid imaging data or genetic ancestry groups were distributed, so it's unclear whether these new associations apply equally across all the ethnic groups included.
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 55 of the 96 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 4 / 4 | 13,409 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 57 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.4 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 3 / 4 | Cited 54 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 28 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37101235) |
| Free to read | 2 / 2 | Free to read |
| Points | 55 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 55 of the 96 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
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