Considerations for Design and Analysis of DNA Methylation Studies

The number of epigenetic studies is exponentially increasing. There is anticipation that DNA methylation may close gaps in our understanding of disease etiology, and how certain risk factors affect health and disease, but also that it has potential as a biomarker for disease. Human DNA methylation studies require careful considerations for design and analysis including population and tissue selection, population stratification, cell heterogeneity, confounding, temporality, sample size, appropriate statistical analysis, and validation of results. In this chapter, we discuss relevant aspects for the design of DNA methylation studies and delineate essential steps for their analysis. Specifically, we summarize methods used to extricate biologic signals from technical noise, and statistical approaches to capture meaningful variability based on the research hypothesis.