Researchers at the Children’s Hospital of Philadelphia (CHOP) have developed a new tool, the Methylation Screening Array (MSA), to explore DNA methylation-mediated regulation of genes. This innovation is intended to shed light on complex human traits such as aging and disease risk. The findings, which are detailed in Cell Genomics, represent the first data set to dissect two forms of DNA methylation—5-methylcytosine and 5-hydroxymethylcytosine.
Epigenome-wide association studies (EWASs) are becoming crucial for understanding the connection between epigenetics and complex human traits. These studies provide insights into how changes in DNA affect health, behavior, or disease risk. Previous tools had limitations that this new dataset aims to overcome.
“Our dataset introduces a focused, scalable, and biologically nuanced tool for epigenetic screening,” said Wanding Zhou, PhD, a lead study author and computational scientist in CHOP’s Center for Computational and Genomic Medicine. “The MSA opens the door for exploring epigenetic mechanisms across tissues, aging, environmental exposures and diverse populations.”
The researchers conducted extensive meta-analyses of human EWASs to develop the MSA for screening trait epigenetic associations. The MSA measures subtle DNA changes by detecting three key forms of cytosine—unmodified, 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC).
Based on their dataset, they characterized tissue-specific methylation biology and trait associations with genetic and epigenetic variations. They integrated MSA data with existing models to predict human traits accurately.
The study also revealed that the epigenetic marker 5hmC varies widely between tissues and plays a significant role in aging processes. The 5hmC-aging EWAS found both universal and tissue-specific methylation changes with age.
CHOP led the design, analysis, software development, paper drafting, and revision efforts with support from researchers at the Perelman School of Medicine at the University of Pennsylvania.
Funding was provided in part by several National Institute of Health grants: P30 AI045008, P30 CA016520, SCR 022380, R35-GM146978, and R01-HG010646.
Goldberg et al.’s study titled “Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits” is available online as of July 3, 2025.
