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The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)
Wolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, Bis JC, Harris TB et al.. PloS one, 2019-07-29
Topic: Risk, prevention and care in population studies
Background Apolipoprotein E is a glycoprotein best known as a mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-ε2 allele on diseases in the elderly and survival remains elusive. Methods We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-ε2, with survival in the population.
Key findings
- The APOE-ε4 allele has long been associated with increased risks of Alzheimer's disease and mortality, but the effect of the less prevalent APOE-ε2 allele on diseases in the elderly and survival remains elusive.
- Methods We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six population-based cohort studies (Rotterdam Study, AGES-Reykjavik Study, Cardiovascular Health Study, Health-ABC Study, and the family-based Framingham Heart Study and Long Life Family Study) to determine the association of APOE, and in particular APOE-ε2, with survival in the population.
- Results During a mean follow-up of 11.7 years, 17,021 individuals died.
- Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P = 1.1*10-2), whereas APOE-ε4 carriers were at increased risk of death (HR 1.17,1.12-1.21; P = 2.8*10-16).
Why it matters
This study combined data from 38,537 people across six population-based cohorts to examine how APOE genotypes, particularly the less common APOE-ε2 allele, relate to survival. The APOE-ε4 allele was already known to increase risks of Alzheimer's disease and mortality, but the effect of APOE-ε2 on diseases in the elderly and survival was less clear.
Study details
- Study designcohort study
- Participants38,537
- Effect size55.6%; HR 1.17; HR 0.89
- Evidence strengthModerate
How this study scored 71/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 68 of the 96 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PloS one) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 4 / 4 | 38,537 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 75 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.3 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 9.1× 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 | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31356640) |
| Free to read | 2 / 2 | Free to read |
| Points | 68 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 68 of the 96 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Wolters, F. J., Yang, Q., Biggs, M. L., Jakobsdottir, J., Li, S., Evans, D. S., et al. (2019). The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE). PloS one. https://doi.org/10.1371/journal.pone.0219668
Vancouver
Wolters FJ, Yang Q, Biggs ML, Jakobsdottir J, Li S, Evans DS, et al. The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE). PloS one. 2019. doi:10.1371/journal.pone.0219668. PMID: 31356640.
BibTeX
@article{wolters2019-31356640,
author = {Wolters, F. J. and Yang, Q. and Biggs, M. L. and Jakobsdottir, J. and Li, S. and Evans, D. S. and Bis, J. C. and Harris, T. B. and others},
title = {{The impact of APOE genotype on survival: Results of 38,537 participants from six population-based cohorts (E2-CHARGE)}},
journal = {PloS one},
year = {2019},
doi = {10.1371/journal.pone.0219668},
pmid = {31356640},
url = {https://doi.org/10.1371/journal.pone.0219668}
}
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