To highlight VMRs enriched for environmental influence, we focused on the top 1% VMRs and looked for ancestry-associated DMRs within these genomic regions. Consistent with the differential expression analysis, we found local ancestry DMRs enriched for genomic regions linked to immune functions. Using VMRs as an environmental proxy to examine the effect of environmental exposures on DEGs, we found that they explained, on average, roughly 15% of population differences in gene expression. Although we used local ancestry to adjust for genetic background, we cannot confirm that methylation variation is solely attributed to environmental factors nor can we ensure that methylation captures all environmental factors. A limitation of this study is the lack of social determinants of health information, which could have directly measured specific environmental exposures instead of using DNA methylation as a proxy. Nevertheless, our analyses demonstrate the potential to limit the impact of systematic environmental factors by leveraging admixture populations for genetic ancestry analyses.
