ArticlePLoS genetics2014
Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Evaluation of the Genetic Variance of Alzheimer's Disease Explained by the Disease-Associated Chromosomal Regions.Journal of Alzheimer's disease : JAD · 2019Pooled it
- Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.PLoS genetics · 2016Pooled it
- Construction of an explainable machine learning model based on SHAP for predicting cardiovascular mortality risk among American cancer survivors.Discover oncology · 2026Article
- Is the Relationship Between Cardiovascular Disease and Alzheimer's Disease Genetic? A Scoping Review.Genes · 2024Article
- How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.Frontiers in aging · 2024Article
- APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.Aging cell · 2022Article
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Likelihood ratio statistics for gene set enrichment in Alzheimer's disease pathways.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Healthy aging and the blood-brain barrier.Nature aging · 2021Review
- APOE4 Copy Number-Dependent Proteomic Changes in the Cerebrospinal Fluid.Journal of Alzheimer's disease : JAD · 2021Article
- APOE2: protective mechanism and therapeutic implications for Alzheimer's disease.Molecular neurodegeneration · 2020Review
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- The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE).PloS one · 2019Article
- Genetic Variation in FOXO3 is Associated with Self-Rated Health in a Population-Based Sample of Older Individuals.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Article
- The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study.PloS one · 2018Article
- Age stratification corrects bias in estimated hazard ofAlzheimer's & dementia (New York, N. Y.) · 2018Article
- Identification of polymorphisms in cancer patients that differentially affect survival with age.Aging · 2017Article
- Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Genome-wide significant risk factors for Alzheimer's disease: role in progression to dementia due to Alzheimer's disease among subjects with mild cognitive impairment.Molecular psychiatry · 2017Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham Heart Study (FHS) original and offspring cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND). The analyses show that women's lifespan is more sensitive to the e4 allele than men's in all these populations. A highly significant adverse effect of the e4 allele is limited to women with moderate lifespan of about 70 to 95 years in two FHS cohorts and the LLFS with relative risk of death RR = 1.48 (p = 3.6 × 10(-6)) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans increasing the risks of death of the e4 carriers with cancer two-fold compared to the non-e4 carriers, i.e., RR = 2.07 (p = 5.0 × 10(-7)). The results suggest a pivotal role of non-sex-specific cancer as a nonlinear modulator of survival in this sample that increases the risk of death of the ApoE4 carriers by 150% (p = 5.3 × 10(-8)) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can non-additively interfere with cancer-related mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.