Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older People
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Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.
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The proportions of APOE genotypes in the CTE sample were significantly different from those found in an age-matched normative sample.
“The proportions of APOE genotypes (i.e., e4 homozygotes, combined e4 homozygotes and heterozygotes, and e4 noncarriers) in our CTE sample were significantly different from those found in an age-matched normative sample 17 (x 2 [2] 5 6.63, p , 0.05).”
From Clinical presentation of chronic traumatic encephalopathy (2013) · cites this paper as [17]
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- Authors
- McKay, G. J., Silvestri, G., Chakravarthy, U., Dasari, S., Fritsche, L. G., Weber, B. H., Keilhauer, C. N., Klein, M. L., Francis, P. J., Klaver, C. C., Vingerling, J. R., Ho, L., De Jong, P. T. D. V., Dean, M., Sawitzke, J., Baird, P. N., Guymer, R. H., Stambolian, D., Orlin, A., Seddon, J. M., Peter, I., Wright, A. F., Hayward, C., Lotery, A. J., Ennis, S., Gorin, M. B., Weeks, D. E., Kuo, C.-L., Hingorani, A. D., Sofat, R., Cipriani, V., Swaroop, A., Othman, M., Kanda, A., Chen, W., Abecasis, G. R., Yates, J. R., Webster, A. R., Moore, A. T., Seland, J. H., Rahu, M., Soubrane, G., Tomazzoli, L., Topouzis, F., Vioque, J., Young, I. S., Fletcher, A. E., & Patterson, C. C.
- Affiliations
- Queen's University Belfast (GB)
- University of Ulster (GB)
- Corresponding author
- McKay, G. J.
- ORCID
- McKay, G. J.
- Silvestri, G.
- Chakravarthy, U.
- Fritsche, L. G.
- Weber, B. H.
- Francis, P. J.
- Klaver, C. C.
- Vingerling, J. R.
- Dean, M.
- Sawitzke, J.
- Baird, P. N.
- Guymer, R. H.
- Seddon, J. M.
- Hayward, C.
- Lotery, A. J.
- Ennis, S.
- Gorin, M. B.
- Weeks, D. E.
- Kuo, C.-L.
- Hingorani, A. D.
- Sofat, R.
- Cipriani, V.
- Swaroop, A.
- Othman, M.
- Kanda, A.
- Chen, W.
- Abecasis, G. R.
- Yates, J. R.
- Webster, A. R.
- Moore, A. T.
- Rahu, M.
- Topouzis, F.
- Young, I. S.
- Fletcher, A. E.
- Patterson, C. C.
- Venue
- American Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04-15
- Volume
- 173
- Issue
- 12
- Pages
- 1357-1364
- ISSN
- 0002-9262 (ISSN-L)
- 1476-6256
- PMC
- PMC3145394
- OpenAlex
- W2150396276
- Cited by
- 105
- References
- 41
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 3 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 14 · 2014: 14 · 2013: 4 · 2012: 11
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- American Journal of Epidemiology (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- University of Pennsylvania
- Tufts Medical Center
- University of Pittsburgh
- School of Public Health, University of Michigan
- National Institute for Health and Care Research (NF-SI-0507-10094)
- University of Southampton
- University College London
- Queen's University Belfast
- Universiteit van Amsterdam
- Queen's University
- Universitetet i Bergen
- Universität Regensburg
- Moorfields Eye Hospital NHS Foundation Trust
- University of California, Los Angeles
- Graduate School of Public Health, University of Pittsburgh
- Tufts University School of Medicine
- Medical Research Council
- Economic and Social Research Council (ES/G007438/1)
- Cambridge Institute for Medical Research, University of Cambridge
- Japan Society for the Promotion of Science (22890007)
- Centre for Public Health, Queen's University Belfast
- National Eye Institute (R01EY011309)
- National Cancer Institute
- David Geffen School of Medicine, University of California, Los Angeles
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- apolipoprotein E, APOE ε4, APOE ε3, APOE ε2, age-related macular degeneration, longevity, allele frequency, older adults, European ancestry
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Apolipoproteins E, Female, Gene Frequency, Humans, Longevity, Macular Degeneration, Male, Middle Aged, White People
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