The DOI matches its Crossref record; 106 of the 107 references it cites were found in a registry or an index.
Worldwide allele frequencies of the human apolipoprotein E gene: Climate, local adaptations, and evolutionary history
Abstract
The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with increased cholesterol levels and heart disease. Population allele frequencies of APOE have previously been shown to vary, with epsilon4 frequencies generally increasing with latitude. We hypothesize that this trend resulted from natural selection protecting against low-cholesterol levels. In high-latitude cold environments and low-latitude hot environments, metabolic rate is elevated, which could require higher cholesterol levels. To explore this hypothesis, we compiled APOE allele frequencies, latitude, temperature, and elevation from populations around the world. epsilon4 allele frequencies show a curvilinear relationship with absolute latitude, with lowest frequencies found in the mid-latitudes where temperatures generally require less expenditure on cooling/thermogenesis. Controlling for population structure in a subset of populations did not appreciably change this pattern of association, consistent with selection pressures that vary by latitude shaping epsilon4 allele frequencies. Temperature records also predict APOE frequency in a curvilinear fashion, with lowest epsilon4 frequencies at moderate temperatures. The model fit between historical temperatures and epsilon4 is less than between latitude and epsilon4, but strengthened after correcting for estimated temperature differences during the Paleolithic. Contrary to our hypothesis, we find that elevation did not improve predictive power, and an…
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“First, the degree of risk and protection afforded by E4 and E2 respectively vary according to ancestry1,59–62.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [62]
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Apolipoprotein E in lipid metabolism and neurodegenerative disease
Yang, L. G., March, Z. M., Stephenson, R. A., & Narayan, P. S. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.05.002 · Cited by 286
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Metadata
- Authors
- Eisenberg, D. T. A., Kuzawa, C. W., & Hayes, M. G.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Eisenberg, Dan T.A.
- Venue
- American Journal of Physical Anthropology
- Publisher
- Wiley
- Published
- 2010-08-16
- Volume
- 143
- Issue
- 1
- Pages
- 100-111
- ISSN
- 0002-9483 (ISSN-L)
- 1096-8644
- OpenAlex
- W2105102381
- Cited by
- 231
- References
- 107
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 11 · 2023: 13 · 2022: 13 · 2021: 22 · 2020: 16 · 2019: 15 · 2018: 14 · 2017: 14 · 2016: 18 · 2015: 15 · 2014: 12 · 2013: 12 · 2012: 16
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physical Anthropology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- U.S. Geological Survey
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- apolipoprotein E, APOE ε4, allele frequency, latitude, temperature, altitude, natural selection, local adaptation, human evolution, cholesterol, metabolic rate, thermogenesis, population structure
- MeSH terms
- Adaptation, Biological, Apolipoproteins E, Basal Metabolism, Cholesterol, Climate, Biological Evolution, Gene Frequency, Genetics, Population, Geography, Humans, Regression Analysis, Selection, Genetic, Temperature, Databases, Genetic
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