Accurate measurement of DNA methylation provides the potential for a molecular record of response to the environment. Development of novel array technology for surveying CpG methylation across the genome has led to an explosion in the study of the relationship between the epigenome and behavior. While these arrays can be used with any tissue type, the most common use is in whole blood samples. Consequently, our discussion here assumes use of whole blood samples. Epigenomic microarray data present a set of additional challenges beyond those posed by genetic microarray data. Comprehensive discussion is presented elsewhere but, in short, quality assessment, scaling and normalization, and removal of batch and other technical artifacts must be performed prior to analysis using packages such as minfi (Aryee et al., 2014). A particularly important aspect of methylation analysis is the removal confounding due to cellular heterogeneity. Importantly, even within a sample of lymphocytes, each cell type (e.g., B cell, T cell, NK cell) will have a unique epigenomic profile and heterogeneity in the relative cell proportions between individuals can lead to spurious results. Cellular heterogeneity
