Leveraging the urban-rural divide for epigenetic research

Urbanization coincides with a complex change in environmental exposure and a rapid increase in noncommunicable diseases (NCDs). Epigenetics, including DNA methylation (DNAm), is thought to mediate part of the association between genetic/environmental exposure and NCDs. The urban-rural divide provides a unique opportunity to investigate the effect of the combined presence of multiple forms of environmental exposure on DNAm and the related increase in disease risk. This review evaluates the ability of three epidemiological study designs (migration, income-comparative and urban-rural designs) to investigate the role of DNAm in the association between urbanization and the rise in NCD prevalence. We also discuss the ability of each study design to address the gaps in the current literature, including the complex methylation-mediated risk attributable to the cluster of forms of exposure characterizing urban and rural living, while providing a platform for developing countries to leverage their demographic discrepancies in future research ventures.