The impact of lifestyle changes on the epigenome

A group’s way of life shapes its gene pool over many generations by selecting for or against different traits. But, because genetic changes require time, a quick switch in lifestyle can lead to a gene-environment mismatch, where genes that were previously advantageous become neutral or harmful. A more rapid adaptive response to such challenges can emerge through epigenetic modifications, which do not alter the DNA sequence, but modify gene expression. To understand how humans respond to rapid lifestyle changes, this study compares individuals with shared ancestry that have and have not undergone such process. The study assesses the regulatory effect of lifestyle on the epigenome, the impact of the gene-environment mismatch on biological aging, and can inform research about how future populations may adapt to lifestyle changes. The study builds upon existing collaborations and provides training opportunities for students. Applying biotechnology methods, the study collects gene expression data and estimates genome expression values. Differential genome-wide methylation is assessed, and methylation differences are quantified. Differentially expressed genes, and differentially methylated sites and regions are identified. All analyses control for relatedness between individuals, population admixture, and differential coverage. Biological aging is estimated using four methods: an elastic net regression model, and three epigenetic clocks. Biological age is assessed in relation to differences in gene expression and methylation patterns. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.