Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history.
Level 4 - case-series / case-control
Ecological cross-sectional population study (graded by design analogy, not clinical CEBM)
PubMed 20734437 · doi:10.1002/ajpa.21298
What was done
The authors compiled global population allele frequencies for apolipoprotein E (APOE) along with geographic and climatic variables (absolute latitude, elevation, modern temperatures, and estimated Paleolithic temperatures). They tested whether climatic variation predicts APOE epsilon4 distribution and evaluated potential confounding by controlling for population structure in a subset of populations.
What was found
The abstract presents no specific numerical statistics, effect estimates, or sample counts. It describes a curvilinear relationship between APOE epsilon4 allele frequency and absolute latitude, with the lowest frequencies occurring in mid-latitudes. Temperature also showed a curvilinear association with epsilon4 frequency, which improved after accounting for estimated Paleolithic temperatures. Controlling for population structure did not alter the latitude association. In contrast to the authors' hypothesis, elevation did not improve predictive power, and an integrated multi-allele cholesterol score showed a weaker association with latitude than epsilon4 alone.
Why it matters
This study evaluates whether human APOE geographic variation reflects climate-driven metabolic adaptation to thermal extremes rather than neutral demographic history alone, offering mixed observational support for climate-mediated selection.
Limits
The abstract provides no sample sizes (number of populations or individuals analyzed) or quantitative statistical metrics. The study is an ecological association analysis reliant on estimated historical climate reconstructions, and key hypotheses regarding elevation and combined-allele cholesterol effects were not supported.
Cited by
- supports Approximately 25% of the human population carries an APOE4 allele.