The platform for epigenome-wide DNAm quantification utilizes the high throughput technology Illumina Methylation Assay. In the past, the 27k Illumina array covered on average two CpG sites in the promoter regions of approximately 14,000 genes and represented less than 0.1% of the 28 million CpG sites in the human genome. This falls short of being representative of the entire human epigenome. None of the early EWAS using this array used independent validation to verify the associated probes. An interesting observation was a bias in the differences between cases and controls towards non-CpG island probes (which were significantly underrepresented in this array design), arguing strongly for the use of the latterly designed 450k array which does cover non-CpG islands with a higher density of probes. Presently, the Illumina 450k array is the most widely used platform in the last two years for studies reporting EWAS. The array still only covers less than 2% of the CpG sites in the genome, but does attempt to cover all known genes with a high density of probes in the promoters (including CpG islands and surrounding sequences), but also covers with a lower density across the gene bodies, 3′ untranslated regions, and other intergenic sequences.
