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.

Incorporating local ancestry improves identification of ancestry-associated methylation signatures and meQTLs in African Americans

“…The downstream analyses of the DNA methylation sites identified across the three approaches to approximate ancestry, demonstrate that ancestry-associated DNA methylation is, on average, highly heritable and significantly depleted in promoter regions (1st Exon, 5′UTR, and TSS200) and CpG islands while moderately enriched in south shores. This agrees with the previous findings of Rawlik et al that population-specific methylations is depleted in promoter regions and CpG islands while enriched in the intergenic region 21 . Moreover, Huan et al also showed that heritable DNA methylation sites are depleted in promoter, TSS200, CpG island, and high-CpG dense regions while enriched in enhancer regions 33 .…”

“…Our findings are based on bulk (i.e., whole blood, peripheral blood mononuclear cells) DNA methylation signatures that were generated from biospecimens collected from VACS and WIHS participants. Despite that one previous study suggested that population-specific methylation signatures are consistent across tissues 21 , examination of cell type-specific ancestral effects on DNA methylation is warranted. Finally, we only examined cis-meQTL in a 1 Mb flanking region of the ancestry-associated CpG site.…”

“…Galanter et al showed that the effects of GA on DNA methylation were partially attributed to cis-acting LA and estimated that LA explained a median of 10% of the variations in GA-associated DNA methylation 30 . Rawlik et al investigated tissue-specific effects of LA on DNA methylation, identifying 552 CpG sites in whole blood and 337 CpG sites in colorectal tissue from Colombian individuals 21 . Although LA analysis of DNA methylation has the potential to capture heterogeneity in genetic admixture with high resolution, there remain few exemplars incorporating LA into EWAS, and no study could be identified that empirically compares the impact of how ancestry is estimated (i.e., self-reported race, GA, and LA) on EWAS findings.…”

A biosocial return to race? A cautionary view for the postgenomic era

“…The studied populations largely mirrored the geographic affiliations of the authors: a large proportion of the 49 studies focused on health inequality within racially defined US African American (66%) and Hispanic American (22%) samples. Other studies addressed Indian (2%), Chinese (2%), and South African ethnic divisions (4%), while a study from the UK addressed admixed individuals from Colombia (Rawlik et al, 2017 ), and one from Poland (Daca‐Roszak et al, 2020 ) focused on differences between samples of European and Chinese ancestry. iv In terms of sex and age, more than half of the participants were of mixed sex (both men and women) (53%), followed by studies on women only (27%), men‐only (10%), and infants and children (10%).…”

“…Despite heterogeneities in methodology and geographic focus, all 49 studies mirror the growing perception that epigenetic markers, and particularly DNA methylation (98%; along with one including RNA non‐coding, Li et al, 2020 ), are a potential basis for explaining ethnic or race‐based differences in health, disease incidence, aging, or reactions to exposures or drugs (Adkins et al, 2011 ; Barfield et al, 2014 ; Davis Lynn et al, 2019 ; Heyn et al, 2013 ; Li et al, 2020 ; Needham et al, 2015 ; Rai et al, 2019 ; Rawlik et al, 2017 ; Song et al, 2015 ). As one study claims, “DNA methylation diversity is a source of variability in human groups at macro and microgeographical scales” (Giuliani et al, 2016 ; similarly McKennan et al, 2020 ) and, given that it is considered “highly divergent between populations” (Fraser et al, 2012 ) can be used to elucidate variation in biological traits or different effects of environmental exposures on racially defined populations: That is, using the terminology of these studies, African American, European, Caucasians (sic), Hispanic, Chinese, or Western (see Table S1 , column 3 for complete overview).…”