The Number of Trait Loci in Late-Onset Alzheimer Disease
Open accessAbstract
Although it is clear that apoE plays an important role in the genetics of late-onset Alzheimer disease (AD), evidence exists that additional genes may play a role in AD, and estimates of the total contribution of apoE to the variance in onset of AD vary widely. Unfortunately, little information is available on the number and contribution of additional genes. We estimated the number of additional quantitative-trait loci and their contribution to the variance in age at onset of AD, as well as the contribution of apoE and sex, in an oligogenic segregation analysis of 75 families (742 individuals) ascertained for members with late-onset AD. We found evidence that four additional loci make a contribution to the variance in age at onset of late-onset AD that is similar to or greater in magnitude than that made by apoE, with one locus making a contribution several times greater than that of apoE. Additionally, we confirmed previous findings of a dose effect for the apoE varepsilon4 allele, a protective effect for the varepsilon2 allele, evidence for allelic interactions at the apoE locus, and a small protective effect for males. Furthermore, although we estimate that the apoE genotype can make a difference of </=17 years in age at onset of AD, our estimate of the contribution of apoE (7%-9%) to total variation in onset of AD is somewhat smaller than that which has previously been reported. Our results suggest that several genes that have not yet been localized may play a larger role…
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Multiple loci are thought to contribute to the onset of Alzheimer's disease.
“Multiple loci are thought to contribute to the onset of AD.”
From Association of rare <i>APOE</i> missense variants with Alzheimer's disease in the Japanese population (2025) · cites this paper as [2]
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- Authors
- Daw, E. W., Payami, H., Nemens, E. J., Nochlin, D., Bird, T. D., Schellenberg, G. D., & Wijsman, E. M.
- Affiliations
- University of Washington (US)
- Oregon Health & Science University (US)
- VA Puget Sound Health Care System (US)
- Corresponding author
- Daw, E. Warwick
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 66
- Issue
- 1
- Pages
- 196-204
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1288326
- OpenAlex
- W2012733162
- Cited by
- 295
- References
- 6
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 33 · 2019: 3 · 2017: 6 · 2016: 6 · 2015: 2 · 2014: 8 · 2013: 11 · 2012: 9
- FWCI
- 12.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 08017, AG 05136, P30AG008017, P50AG005136, U24AG021886)
- National Institute of General Medical Sciences (R01GM046255, GM46255, R37GM046255)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- late-onset Alzheimer's disease, quantitative trait loci, apolipoprotein E, APOE ε4, APOE ε2 allele, age of onset, sex differences, allelic interaction, familial Alzheimer's disease
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Female, Genotype, Humans, Male, Middle Aged, Monte Carlo Method, Sex Factors, Survival Analysis, Age of Onset, Quantitative Trait, Heritable
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