Worldwide Distribution of the Human Apolipoprotein E Gene - The Association between APOE, Subsistence, and Latitude

Date of Award

Fall 1-18-2018

Document Type


Degree Name

Master of Arts (MA)



First Advisor

Michael Steiper

Second Advisor

Herman Pontzer

Academic Program Adviser

Yukiko Koga


The human apolipoprotein E gene (APOE) plays an important role in metabolizing lipids, regulating plasma cholesterol, and maintaining biological function. Structural differences in APOE variants impact cholesterol absorption and health risk, so that alleles serve as biomarkers for numerous cardiovascular and neurological diseases (Lai 2015). Variant differences are determined by changes in two single nucleotide polymorphisms (SNPs), rs429358 and rs7412. Distribution of alleles varies across populations. Allele frequencies in populations have been shown to be associated with cultural and environmental factors, including subsistence strategy and latitude (Eisenberg 2010).

This study aims to provide a cross-population, genetic association study between APOE, subsistence strategy, and latitude. The objective of the study is to examine the roles that subsistence and latitude have in shaping APOE allele frequencies within populations. The study hypothesizes that E3 correlates with agriculture / post-agriculture and low latitude, and E4 correlates with non-agricultural and high latitude. The study further predicts that E2 is not linked to either subsistence or latitude.

To test these hypotheses, genotype data on 124 APOE SNPs, and subsistence and latitude data was compiled for 26 populations. The data were adjusted for population stratification, and remaining SNPs were tested for significance based on linkage between loci. Afterward, subsistence and latitude were first tested as independent variables for an association with each SNP / haplotype, then as covariates.

Results on the associations between APOE and subsistence and latitude were mixed. SNPs rs429358 and rs7412 were confirmed to be significant in determining APOE variation. Association results on each SNP showed a link between rs429358 and subsistence, and latitude, as well as between rs7412 and latitude – but not between rs7412 and subsistence. Association results on haplotypes confirmed the hypothesis that subsistence and latitude each play a role in APOE distribution – although this role lessened when considering the other variable. When subsistence and latitude were treated as independent variables, E3 showed an association with both subsistence and latitude. Yet, the correlation between E3 and subsistence disappeared when latitude was a covariate. Further, while E4 was confirmed to be associated with subsistence, this association decreased when latitude was a covariate.

The study also confirmed the subsistence hypotheses, with E3 linked to post-agriculture (when subsistence was an independent variable) and E4 linked to non-agriculture. However, the study refuted the latitude hypotheses by showing a reverse association than predicted, with E3 being associated with high latitude and E4 being associated with low latitude. Also, contrary to the hypotheses, E2 was shown to be associated with both subsistence and latitude. In summary, results from the study support an association between APOE, subsistence, and latitude; however, the results do not support the direction of association between specific APOE alleles and these variables.

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