Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity
Rogaeva E, Premkumar S, Song Y, Sorbi S, Brindle N, Paterson A, Duara R, Levesque G et al.. JAMA, 1998-08-01
Topic: Amyloid, tau and blood-test diagnosis
Context Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12. Objective To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases. Design Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) epsilon4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives. Setting Clinical populations in the continental United States, Canada, Argentina, and Italy. Patients Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives. Main outcome measure Presence of an APOE epsilon4 allele among affected family members. Results Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P Conclusions Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Rogaeva, E., Premkumar, S., Song, Y., Sorbi, S., Brindle, N., Paterson, A., et al. (1998). Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA. https://doi.org/10.1001/jama.280.7.614
Vancouver
Rogaeva E, Premkumar S, Song Y, Sorbi S, Brindle N, Paterson A, et al. Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA. 1998. doi:10.1001/jama.280.7.614. PMID: 9718052.
BibTeX
@article{rogaeva1998-9718052,
author = {Rogaeva, E. and Premkumar, S. and Song, Y. and Sorbi, S. and Brindle, N. and Paterson, A. and Duara, R. and Levesque, G. and others},
title = {{Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity}},
journal = {JAMA},
year = {1998},
doi = {10.1001/jama.280.7.614},
pmid = {9718052},
url = {https://doi.org/10.1001/jama.280.7.614}
}
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Key findings
- Results Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families.
- However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1).
Why it matters
In 53 families with multiple members affected by Alzheimer's disease, this study found no evidence for linkage to chromosome 12 markers when assuming all families share the same genetic locus. However, significant evidence for linkage appeared when allowing for locus heterogeneity, supporting the idea that more than one gene may be involved.
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Study details
- Study designcohort study
- Participants173
- Evidence strengthModerate
How this study scored 60/100
Published in a top-tier journal, and it is a cohort study following people over time. Scored zero for effect reported and randomized / blinded 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 | 7 / 12 | A cohort study following people over time |
| 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 | 1998 — older than 20 years, still counted |
| Sample size | 2 / 4 | 173 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 151 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 4 / 6 | Cited 12.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ekaterina A. Rogaeva: h-index 93 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9718052) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
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