A Cross-Platform Genome-Wide Comparison of the Relationship of Promoter DNA Methylation to Gene Expression

Peripheral mononuclear cell preparations are commonly used as proxies for other tissues in studies of the role of gene expression and methylation in human disease. Whether changes in peripheral DNA methylation are associated with changes in peripheral blood or brain gene expression is not clear. In order to test the former hypothesis and determine which genome-wide methylation platform was most suitable for our studies of peripheral blood cells, we compared the results from two commercially available genome-wide methylation arrays with respect to genome-wide gene expression using lymphoblast DNA and RNA from eight individuals at the promoters of 5619 genes. We found that methylation signatures at these gene promoters were significantly correlated with one another across platforms and with genome-wide gene expression, but the extent of that relationship is dependent on choice of platform and degree of methylation. Taken in context with data from other studies, these data demonstrate that peripheral blood cell methylation is associated with gene expression and that further studies to clarify the extent of this relationship, and the relationship between central and peripheral DNA methylation are in order.