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VCU Team Wins $3M to Search for Biomarkers Caused by Childhood Adversity

NEW YORK (GenomeWeb) – Researchers at Virginia Commonwealth University have reeled in a $3 million grant from the National Institute of Mental Health to investigate whether adverse experiences during childhood leave molecular marks that potentially could be used in diagnostic tests to predict health risks later in life, VCU said yesterday.

Investigators at VCU's Center for Biomarker Research and Personalized Medicine will work with partners at the Duke University School of Medicine to study how severe illnesses, neglect, and maltreatment that occur during childhood may impact DNA methylation.

The foundation for this project, which is led by the personalized medicine center's director Edwin van den Oord, is the longitudinal Great Smoky Mountain Study that began at Duke 20 years ago by looking at nine- to 13-year-old children. That study, which today continues following its participants into their thirties, has taken detailed assessments and blood samples at two-year intervals, and will enable researchers to compare DNA methylation profiles before and after adverse events and connect their findings to health outcomes later in life.

"Childhood adverse experiences such as severe illness, neglect, or maltreatment have been robustly linked to psychiatric and other medical conditions where the consequences often persist far into adulthood," van den Oord said in a statement. "Our goal is to study how these early adverse experiences become biologically embedded and how they create long-term health risks."

Two out of three children by age 16 have experienced at least one adverse experience, and these have been strongly linked to an array of psychiatric and other medical conditions that persist into adulthood, the VCU team said in the project proposal.

Because DNA methylation occurs mainly in CpG sites in the human genome – sites where a cytosine and guanine nucleotide occur next to each other – the researchers will use next-generation sequencing to assay all of the roughly 28 million CpGs in the human genome to look for adversity-induced methylation changes and their persistence over time. They plan to investigate methylation sites that changed as a result of adversity and then associate those sites with health risks. The researchers also plan to replicate the top 175 findings in independent samples using a different targeted technology to minimize the risk of false positives.

"DNA methylation can be measured cost-effectively and blood samples are relatively easy to collect. The study could therefore result in biomarkers that can be used in the clinic to assess the biological impact of childhood adversity to help better manage health risks," van den Oord said.