mCSEA: Identification of subtle differential methylation in predefined regions. Studying the epigenomics of fetal growth disorders

Abstract

DNA methylation is the most studied epigenetic mark. It affects gene expression and has an im-portant role in several disorders. EWAS are performed to find associations between DNA methylation alterations and a given phenotype. Although there are several tools to perform EWAS, currently all of them are focused on detecting relatively large differences in methylation levels between phenotypes. However, some complex disorders are associated to moderate, but consistent, methylation changes. We developed mCSEA, an approach consisting in the application of the Gene-Set Enrichment Analy-sis methods to detect subtle methylation differences in predefined regions. We applied mCSEA to perform an EWAS with 103 placental samples from SGA, AGA and LGA children. We discovered several known and unknown methylation differences in gene promoters associated to birth weight alterations in our cohort. This case study demonstrates the potential of mCSEA to detect very subtle methylation changes. mCSEA method will be implemented and released as an R package in future.