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Worldwide allele frequencies of the human apolipoprotein E gene: Climate, local adaptations, and evolutionary history

Eisenberg, Dan T.A., Kuzawa, Christopher W., Hayes, M. Geoffrey·2010·American Journal of Physical Anthropology

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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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Authors: Eisenberg, D. T. A., Kuzawa, C. W., & Hayes, M. G.
Affiliations: Northwestern University (US)
Corresponding author: Eisenberg, Dan T.A.
ORCID: Eisenberg, Dan T.A.
Kuzawa, Christopher W.
Hayes, M. Geoffrey
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
DOI: 10.1002/ajpa.21298
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Worldwide allele frequencies of the human apolipoprotein E gene: Climate, local adaptations, and evolutionary history

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