Measuring epigenetics as the mediator of gene/environment interactions in DOHaD.

Analysis of DNA methylation data in epigenome-wide association studies provides many bioinformatics and statistical challenges. Not least of these, are the non-independence of individual DNA methylation marks from each other, from genotype and from technical sources of variation. In this review we discuss DNA methylation data from the Infinium450K array and processing methodologies to reduce technical variation. We describe recent approaches to harness the concordance of neighbouring DNA methylation values to improve power in association studies. We also describe how the non-independence of genotype and DNA methylation has been used to infer causality (in the case of Mendelian randomization approaches); suggest the mediating effect of DNA methylation in linking intergenic single nucleotide polymorphisms, identified in genome-wide association studies, to phenotype; and to uncover the widespread influence of gene and environment interactions on methylation levels.