Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans
Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang LS, Valladares O, Lin CF et al.. JAMA, 2013-04-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, setting, and participants The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main outcomes and measures Presence of Alzheimer disease according to standardized criteria. Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 Conclusions and relevance In this meta-analysis of data from African American participants, Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional validation of this finding is needed before this information is used in clinical settings.
Key findings
- Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown.
- Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans.
- Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci.
- Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 < D' < 0.9).
Why it matters
This meta-analysis in African Americans found a genome-wide significant link between a variant in the ABCA7 gene and late-onset Alzheimer's disease. Identifying such variants may help point to targets for genetic testing, prevention, and treatment.
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Study details
- Study designmeta-analysis
- Participants5,896
- Evidence strengthHigh
How this study scored 78/100
Published in a top-tier journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 5,896 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 435 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 29.0 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 5 / 6 | Cited 26.0× 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 | 3 / 4 | Cited 77 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Richard P Mayeux: h-index 158 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 22 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23571587) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 78 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Reitz, C., Jun, G., Naj, A., Rajbhandary, R., Vardarajan, B. N., Wang, L. S., et al. (2013). Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans. JAMA. https://doi.org/10.1001/jama.2013.2973
Vancouver
Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan BN, Wang LS, et al. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013. doi:10.1001/jama.2013.2973. PMID: 23571587.
BibTeX
@article{reitz2013-23571587,
author = {Reitz, C. and Jun, G. and Naj, A. and Rajbhandary, R. and Vardarajan, B. N. and Wang, L. S. and Valladares, O. and Lin, C. F. and others},
title = {{Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans}},
journal = {JAMA},
year = {2013},
doi = {10.1001/jama.2013.2973},
pmid = {23571587},
url = {https://doi.org/10.1001/jama.2013.2973}
}
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