Epigenome-wide association studies (EWAS) profile DNA methylation across the human genome to identify associations with diseases and exposures. Most employ Illumina methylation arrays
this platform, however, under-samples interindividual epigenetic variation. The systemic and stable nature of epigenetic variation at correlated regions of systemic interindividual variation (CoRSIVs) should be advantageous to EWAS. Here, we analyze 2,203 published EWAS to determine whether Illumina probes within CoRSIVs are over-represented in the literature. Enrichment of CoRSIV-overlapping probes was observed for most classes of disease, particularly for neurodevelopmental disorders and type 2 diabetes, indicating an opportunity to improve the power of EWAS by over 200- and over 100-fold, respectively. EWAS targeting all known CoRSIVs should accelerate discovery of associations between individual epigenetic variation and risk of disease.