Topic: Amyloid, tau and blood-test diagnosis
Only Apolipoprotein E polymorphisms have been consistently associated with the risk of late-onset Alzheimer disease (LOAD), but they represent only a minority of the underlying genetic effect. To identify additional LOAD risk loci, we performed a genome-wide association study (GWAS) on 492 LOAD cases and 498 cognitive controls using Illumina's HumanHap550 beadchip. An additional 238 cases and 220 controls were used as a validation data set for single-nucleotide polymorphisms (SNPs) that met genome-wide significance. To validate additional associated SNPs (p < 0.0001) and nominally associated candidate genes, we imputed SNPs from our GWAS using a previously published LOAD GWAS(1) and the IMPUTE program. Association testing was performed with the Cochran-Armitage trend test and logistic regression, and genome-wide significance was determined with the False Discovery Rate-Beta Uniform Mixture method. Extensive quality-control methods were performed at both the sample and the SNP level. The GWAS confirmed the known APOE association and identified association with a 12q13 locus at genome-wide significance; the 12q13 locus was confirmed in our validation data set. Four additional highly associated signals (1q42, 4q28, 6q14, 19q13) were replicated with the use of the imputed data set, and six candidate genes had SNPs with nominal association in both the GWAS and the joint imputated data set. These results help to further define the genetic architecture of LOAD.
Key findings
- Only Apolipoprotein E polymorphisms have been consistently associated with the risk of late-onset Alzheimer disease (LOAD), but they represent only a minority of the underlying genetic effect.
- These results help to further define the genetic architecture of LOAD.
Why it matters
This genome-wide association study confirmed the known APOE link and found a new risk locus on chromosome 12, along with several other signals that were replicated. These results help to further define the genetic architecture of late-onset Alzheimer disease, but they do not by themselves provide a treatment or cure.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American journal of human genetics) |
| Journal's citation record | 3 / 4 | The American Journal of Human Genetics: journal h-index 385 (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 | 1 / 5 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 260 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.7 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 5 / 6 | Cited 25.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 20 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Margaret A. Pericak‐Vance: h-index 114 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Duke University: institution h-index 1,541 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19118814) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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 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.
APA 7th
Beecham, G. W., Martin, E. R., Li, Y. J., Slifer, M. A., Gilbert, JR., Haines, J. L., et al. (2009). Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. American journal of human genetics. https://doi.org/10.1016/j.ajhg.2008.12.008
Vancouver
Beecham GW, Martin ER, Li YJ, Slifer MA, Gilbert JR, Haines JL, et al. Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. American journal of human genetics. 2009. doi:10.1016/j.ajhg.2008.12.008. PMID: 19118814.
BibTeX
@article{beecham2009-19118814,
author = {Beecham, G. W. and Martin, E. R. and Li, Y. J. and Slifer, M. A. and Gilbert, JR. and Haines, J. L. and Pericak-Vance, M. A.},
title = {{Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease}},
journal = {American journal of human genetics},
year = {2009},
doi = {10.1016/j.ajhg.2008.12.008},
pmid = {19118814},
url = {https://doi.org/10.1016/j.ajhg.2008.12.008}
}
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