Although the combined impact of genetic variants on phenotypic traits has become of increased interest over the last few years, there has so far been little research undertaken to understand the combined impact of variants on DNA methylation. We intend to apply collapsing approaches to collapsed methylation scores to investigate this. This could be an attractive approach in contrast to individual CpG site analyses for many reasons, such as computional efficiency, reducing the burden of multiple testing, smoothing out artefacts and representing the underlying biology in a different form by collapsing across functional units (e.g. CpG islands, including/excluding shores, entire promoter regions). Furthermore, the manner in which methylation data is collapsed is an aspect of this work which will need to be evaluated. There are currently some methods out there which could be used for this purpose, although so far they have mainly been used to investigate the relationship between methylation and phenotypic traits.

As pairwise association analyses for individual CpG sites is currently being undertaken using the 450K methylation data in ALSPAC, this should provide a useful comparison for this proposed approach.