Topic: Amyloid, tau and blood-test diagnosis
There has been great interest in the prospects of using single-nucleotide polymorphisms (SNPs) in the search for complex disease genes, and several initiatives devoted to the identification and mapping of SNPs throughout the human genome are currently underway. However, actual data investigating the use of SNPs for identification of complex disease genes are scarce. To begin to look at issues surrounding the use of SNPs in complex disease studies, we have initiated a collaborative SNP mapping study around APOE, the well-established susceptibility gene for late-onset Alzheimer disease (AD). Sixty SNPs in a 1.5-Mb region surrounding APOE were genotyped in samples of unrelated cases of AD, in controls, and in families with AD. Standard tests were conducted to look for association of SNP alleles with AD, in cases and controls. We also used family-based association analyses, including recently developed methods to look for haplotype association. Evidence of association (P</=.05) was identified for 7 of 13 SNPs, including the APOE-4 polymorphism, spanning 40 kb on either side of APOE. As expected, very strong evidence for association with AD was seen for the APOE-4 polymorphism, as well as for two other SNPs that lie <16 kb from APOE. Haplotype analysis using family data increased significance over that seen in single-locus tests for some of the markers, and, for these data, improved localization of the gene. Our results demonstrate that associations can be detected at SNPs near a complex disease gene. We found that a high density of markers will be necessary in order to have a good chance of including SNPs with detectable levels of allelic association with the disease mutation, and statistical analysis based on haplotypes can provide additional information with respect to tests of significance and fine localization of complex disease genes.
Key findings
- Our results demonstrate that associations can be detected at SNPs near a complex disease gene.
- We found that a high density of markers will be necessary in order to have a good chance of including SNPs with detectable levels of allelic association with the disease mutation, and statistical analysis based on haplotypes can provide additional information with respect to tests of significance and fine localization of complex disease genes.
Why it matters
This study genotyped 60 single-nucleotide polymorphisms in a 1.5-Mb region around APOE and found association with Alzheimer disease for 7 of 13 SNPs, including the APOE-4 polymorphism. It is a methods-focused genetic study showing that associations can be detected near a complex disease gene, not a treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 | 2000 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 359 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.8 citations a year over 28 year(s) since 2000 |
| Impact for its field and year | 5 / 6 | Cited 23.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jeffery M. Vance: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Duke University: institution h-index 1,541 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10869235) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 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'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
Martin, E. R., Lai, E. H., Gilbert, JR., Rogala, A. R., Afshari, A. J., Riley, J., et al. (2000). SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. American journal of human genetics. https://doi.org/10.1086/303003
Vancouver
Martin ER, Lai EH, Gilbert JR, Rogala AR, Afshari AJ, Riley J, et al. SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. American journal of human genetics. 2000. doi:10.1086/303003. PMID: 10869235.
BibTeX
@article{martin2000-10869235,
author = {Martin, E. R. and Lai, E. H. and Gilbert, JR. and Rogala, A. R. and Afshari, A. J. and Riley, J. and Finch, K. L. and Stevens, J. F. and others},
title = {{SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease}},
journal = {American journal of human genetics},
year = {2000},
doi = {10.1086/303003},
pmid = {10869235},
url = {https://doi.org/10.1086/303003}
}
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