ABCA7 frameshift deletion associated with Alzheimer disease in African Americans
Cukier HN, Kunkle BW, Vardarajan BN, Rolati S, Hamilton-Nelson KL, Kohli MA, Whitehead PL, Dombroski BA et al.. Neurology. Genetics, 2016-05-17
Topic: Amyloid, tau and blood-test diagnosis
Objective To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42-3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12-2.44]), and joint analysis increased the significance (p = 1.414 × 10(-5), OR = 1.81 [95% CI: 1.38-2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD.
Key findings
- Results A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele.
- The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42-3.20]).
- The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function.
Why it matters
A 44-base pair deletion in the ABCA7 gene was linked to Alzheimer's in African Americans (odds ratio 1.81 across two groups after adjusting for age, sex and APOE). It is predicted to disrupt the ABCA7 protein. It was common in African Americans (15.2% of cases, 9.74% of controls) but found in only 0.12% of the study's non-Hispanic white cohort, which suggests an ancestry-specific risk factor. This is an association: many carriers did not have the disease, and the study does not show a treatment, prevention or test.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Participants1,068
- Effect sizeOR = 1.65; OR = 1.81; 15.2%
- Evidence strengthModerate
How this study scored 54/100
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 (Neurology. Genetics) |
| Journal's citation record | 0 / 4 | Neurology Genetics: journal h-index 53 (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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,068 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 99 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.2 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 5.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Lee‐Way Jin: h-index 32 (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 27231719) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/nxg.0000000000000079
- PubMed: 27231719
- Original source →
- Free full text: Neurology Genetics →
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
Cukier, H. N., Kunkle, B. W., Vardarajan, B. N., Rolati, S., Hamilton-Nelson, K. L., Kohli, M. A., et al. (2016). ABCA7 frameshift deletion associated with Alzheimer disease in African Americans. Neurology. Genetics. https://doi.org/10.1212/nxg.0000000000000079
Vancouver
Cukier HN, Kunkle BW, Vardarajan BN, Rolati S, Hamilton-Nelson KL, Kohli MA, et al. ABCA7 frameshift deletion associated with Alzheimer disease in African Americans. Neurology. Genetics. 2016. doi:10.1212/nxg.0000000000000079. PMID: 27231719.
BibTeX
@article{cukier2016-27231719,
author = {Cukier, H. N. and Kunkle, B. W. and Vardarajan, B. N. and Rolati, S. and Hamilton-Nelson, K. L. and Kohli, M. A. and Whitehead, P. L. and Dombroski, B. A. and others},
title = {{ABCA7 frameshift deletion associated with Alzheimer disease in African Americans}},
journal = {Neurology. Genetics},
year = {2016},
doi = {10.1212/nxg.0000000000000079},
pmid = {27231719},
url = {https://doi.org/10.1212/nxg.0000000000000079}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 19.
Later studies that cite this one
7 studies in the alzhub library list this one in their references.
Related studies in Genetics
Also tagged “amyloid-beta”
1,339 studies in the library carry the topic tag “amyloid-beta”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.