Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans
Rajabli F, Tosto G, Hamilton-Nelson KL, Kunkle BW, Vardarajan BN, Naj A, Whitehead PG, Gardner OK, Bush WS, Sariya S, Mayeux RP, Farrer LA, et al.. Alzheimer's & Dementia, 2022-12-20
Topic: Amyloid, tau and blood-test diagnosis
Background This study used admixture mapping to prioritize the genetic regions associated with Alzheimer's disease (AD) in African American (AA) individuals, followed by ancestry-aware regression analysis to fine-map the prioritized regions. Methods We analyzed 10,271 individuals from 17 different AA datasets. We performed admixture mapping and meta-analyzed the results. We then used regression analysis, adjusting for local ancestry main effects and interactions with genotype, to refine the regions identified from admixture mapping. Finally, we leveraged in silico annotation and differential gene expression data to prioritize AD-related variants and genes. Results Admixture mapping identified two genome-wide significant loci on chromosomes 17p13.2 (p = 2.2 × 10 -5 ) and 18q21.33 (p = 1.2 × 10 -5 ). Our fine mapping of the chromosome 17p13.2 and 18q21.33 regions revealed several interesting genes such as the MINK1, KIF1C, and BCL2. Discussion Our ancestry-aware regression approach showed that AA individuals have a lower risk of AD if they inherited African ancestry admixture block at the 17p13.2 locus. Highlights We identified two genome-wide significant admixture mapping signals: on chromosomes 17p13.2 and 18q21.33, which are novel in African American (AA) populations. Our ancestry-aware regression approach showed that AA individuals have a lower risk of Alzheimer's disease (AD) if they inherited African ancestry admixture block at the 17p13.2 locus. We found that the overall proportion of African ancestry does not differ between the cases and controls that suggest African genetic ancestry alone is not likely to explain the AD prevalence difference between AA and non-Hispanic White populations.
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APA 7th
Rajabli, F., Tosto, G., Hamilton-Nelson, K. L., Kunkle, B. W., Vardarajan, B. N., Naj, A., et al. (2023). Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans. Alzheimer's & Dementia. https://doi.org/10.1002/alz.12865
Vancouver
Rajabli F, Tosto G, Hamilton-Nelson KL, Kunkle BW, Vardarajan BN, Naj A, et al. Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans. Alzheimer's & Dementia. 2023. doi:10.1002/alz.12865. PMID: 36539198.
BibTeX
@article{rajabli2023-36539198,
author = {Rajabli, F. and Tosto, G. and Hamilton-Nelson, K. L. and Kunkle, B. W. and Vardarajan, B. N. and Naj, A. and Whitehead, P. G. and Gardner, O. K. and Bush, W. S. and Sariya, S. and Mayeux, R. P. and Farrer, L. A. and others},
title = {{Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans}},
journal = {Alzheimer's \& Dementia},
year = {2023},
doi = {10.1002/alz.12865},
pmid = {36539198},
url = {https://doi.org/10.1002/alz.12865}
}
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Key findings
- Background This study used admixture mapping to prioritize the genetic regions associated with Alzheimer's disease (AD) in African American (AA) individuals, followed by ancestry-aware regression analysis to fine-map the prioritized regions.
- We performed admixture mapping and meta-analyzed the results.
- Results Admixture mapping identified two genome-wide significant loci on chromosomes 17p13.2 (p = 2.2 × 10 -5 ) and 18q21.33 (p = 1.2 × 10 -5 ).
- Our fine mapping of the chromosome 17p13.2 and 18q21.33 regions revealed several interesting genes such as the MINK1, KIF1C, and BCL2.
- Discussion Our ancestry-aware regression approach showed that AA individuals have a lower risk of AD if they inherited African ancestry admixture block at the 17p13.2 locus.
Why it matters
This study identified two genetic regions on chromosomes 17 and 18 linked to Alzheimer's disease in African American individuals, and found that inheriting African ancestry at the 17p13.2 region was associated with lower risk. These findings highlight genes like MINK1, KIF1C, and BCL2 that may matter for Alzheimer's risk in this population.
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Study details
- Study designcase-control
- Participants10,271
- Evidence strengthModerate
Limitations
Underpowered to detect local-ancestry associations where risk-allele frequencies and effects are similar across ancestral groups; the African American samples were combined into one discovery set and an independent replication dataset is still needed; ancestry-aware fine-mapping was underpowered for the large 18q21.33 region.
How this study scored 59/100
Published in a leading specialty journal, and it is a case-control study. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 58 of the 98 points we could judge it on, which is 59 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 | 6 / 12 | A case-control study |
| 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 | 10,271 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 | 3 / 7 | Cited 15 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Eden R. Martin: h-index 83 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36539198) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 58 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 58 of the 98 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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