Topic: Amyloid, tau and blood-test diagnosis
Objective To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs. Design Case-control study with replication. Setting Memory referral clinics in Canada and the United Kingdom. Participants The hypothesis-generating data set consisted of 753 individuals with AD by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria recruited from 9 memory referral clinics in Canada and 736 ethnically matched control subjects; control subjects were recruited from nonbiological relatives, friends, or spouses of the patients and did not exhibit cognitive impairment by history or cognitive testing. The follow-up data set consisted of 418 AD cases and 249 nondemented control cases from the United Kingdom Medical Research Council Genetic Resource for Late-Onset AD recruited from clinics at Cardiff University, Cardiff, Wales, and King's College London, London, England. Main outcome measures Odds ratios and 95% confidence intervals for association of SNPs with AD by logistic regression adjusted for age, sex, education, study site, and French Canadian ancestry (for the Canadian data set). Hazard ratios and 95% confidence intervals from Cox proportional hazards regression for age at onset with similar covariate adjustments. Results Unadjusted, SNP RS4420638 within APOC1 was strongly associated with AD due entirely to linkage disequilibrium with APOE. In the multivariable adjusted analyses, 3 SNPs within the top 120 by P value in the logistic analysis and 1 in the Cox analysis of the Canadian data set provided additional evidence for association at P Conclusions Our genomewide association analysis again identified the APOE linkage disequilibrium region as the strongest genetic risk factor for AD. This could be a consequence of the coevolution of more than 1 susceptibility allele, such as APOC1, in this region. We also provide new evidence for additional candidate genetic risk factors for AD that can be tested in further studies.
Key findings
- Objective To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs.
- Results Unadjusted, SNP RS4420638 within APOC1 was strongly associated with AD due entirely to linkage disequilibrium with APOE.
Why it matters
This genome-wide association study found that a variant near APOC1 was strongly linked to Alzheimer's disease, but this was due entirely to its linkage with APOE. No other new risk genes were confirmed in the reported findings.
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Study details
- Study designcase-control study
- Participants753
- Evidence strengthModerate
How this study scored 62/100
Published in a peer-reviewed 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 institution's track record, so that was left out: it earned 60 of the 97 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (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 | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 753 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 | 6 / 7 | Cited 501 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.1 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 5 / 6 | Cited 31.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 26 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Allen D. Roses: h-index 94 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17998437) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 60 / 97 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 60 of the 97 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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
Li, H., Wetten, S., Li, L., St Jean, P. L., Upmanyu, R., Surh, L., et al. (2008). Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Archives of neurology. https://doi.org/10.1001/archneurol.2007.3
Vancouver
Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, et al. Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Archives of neurology. 2008. doi:10.1001/archneurol.2007.3. PMID: 17998437.
BibTeX
@article{li2008-17998437,
author = {Li, H. and Wetten, S. and Li, L. and St Jean, P. L. and Upmanyu, R. and Surh, L. and Hosford, D. and Barnes, M. R. and others},
title = {{Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease}},
journal = {Archives of neurology},
year = {2008},
doi = {10.1001/archneurol.2007.3},
pmid = {17998437},
url = {https://doi.org/10.1001/archneurol.2007.3}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
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