Implications of genotype and environment on variation in DNA methylation

Abstract

The epigenome is highly plastic and reacts to the changing external conditions such as diet, lifestyle, and toxins throughout the lifespan. Epigenome-wide association studies (EWAS) provide an opportunity to identify epigenetic variants associated with such exposures and the associated suboptimal health outcomes. DNA methylation at 5-methylcytosine is a routinely interrogated epigenetic mark in such EWAS studies. However, depending upon the choice of biological sample, a reliable quantification of the change in methylome at a genomic locus is often confounded by cellular heterogeneity. In addition, the interpretation of cause and effect of this methylation diversity in epigenomes is further complicated by the contributions from genotype and its interaction with the environment, thereby warranting a more sophisticated approach to reliably measure and interpret EWAS findings. This chapter discusses the factors influencing the variability in DNA methylome and its implications on biological interpretations.