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Cited by 231Genetic Associations and EpidemiologyForensic and Genetic ResearchEvolution and Genetic Dynamics

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

Eisenberg, Dan T.A., Kuzawa, Christopher W., Hayes, M. Geoffrey·2010·American Journal of Physical Anthropology
DOI 10.1002/ajpa.21298
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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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  1. Bellido D, 1993, Perfil lipídico de la población de Viacha, Acta Andina, 2, 28
  2. Eisenberg D, 2009, Evidence for cholesterol function and local climatic adaptation based on worldwide allele frequency variations of the apoliprotein E (APOE) gene, Am J Hum Biol, 21, 253
  3. Ewald P, 2008, Evolutionary medicine and health: new perspectives, 350
  4. Itzhaki RF, 2004, The role of viruses and of APOE in dementia. Strategies for engineered negligible senescence: why genuine control of aging may be foreseeable, 15
  5. Kuzawa CW, 2006, Evolutionary medicine and human cholesterol, Am J Hum Biol, 18, 261
  6. Leininger‐Muller B, 1998, Oxidation of human apolipoprotein E and cerebral enzymatic systems, Alzheimers Rep, 1, 95
  7. 10.1001/archinte.121.5.414 · DOI

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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.
ORCID
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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