Evidence of epigenetic admixture in the Colombian population

Abstract

DNA methylation (DNAm) measured in lymphoblastoid cell lines has been repeatedly demonstrated to differ between various human populations. Due to the role that DNAm plays in controlling gene expression, these differences could significantly contribute to ethnic phenotypic differences. However, because previous studies have compared distinct ethnic groups where genetic and environmental context are confounded, their relative contribution to phenotypic differences between ethnicities remains unclear. Using DNAm assayed in whole blood and colorectal tissue of 132 admixed individuals from Colombia, we identified sites where differential DNAm levels were associated with the local ancestral genetic context. Our results are consistent with population specific DNAm being primarily driven by between population genetic differences in cis, with little environmental contribution, and with consistent effects across tissues. The findings offer new insights into a possible mechanism driving phenotypic differences among different ethnic groups, and could help explain ethnic differences in colorectal cancer incidence.

Figure 1.

Summary of popDNAm sites across both tissues considered. We plot the numbers of sites with significant effects of local ancestry (FDR 1%) for different window sizes used for local ancestry estimation. Specifically, we show the absolute number of popDNAm sites (A) and the number of popDNAm sites as the fraction of sites tested for a specific window size (B).

Figure 2.

Distribution of identified popDNAm sites in the genome. We plot –log₁₀ P value of the likelihood ratio test for presence of effects of local ancestry proportions in a 500kb for each tested DNAm site in colorectum (A) and whole blood (B). Sites which are significant (FDR 1%) are shown in black.

Figure 3.

Across tissue comparison of ancestral population effects at individual popDNAm sites. We plot the estimated effect of local Native American (A) and African (b) ancestry within a 500kb window in whole blood tissue (Blood) versus the effect in colorectal tissue (Colon). Effects are only plotted for sites which, for either tissue, were identified as popDNAm sites based on local ancestry in the 500kb window. Colour indicates for which tissue a specific site was identified as exhibiting popDNAm.

Figure 4.

Enrichment of popDNAm sites in colorectum for genetic context. Specifically, gene context (A) and CpG-Island context (B). We plot the observed fraction of sites associated with a specific context amongst popDNAm sites and the expected such fraction under the assumption that popDNAm sites are randomly distributed amongst all tested sites ($H_0$). Error bars for $H_0$ indicate the empirically estimated 95% interval for this model. Considered popDNAm sites showed a significant effect based on 500kb window in colorectum.