Epigenetic changes at birth linked to metabolic dysfunction in preteens
Key takeaways:
- Researchers found associations between DNA methylation on imprinted genes at birth and metabolic dysfunction in pre-teenage years.
- Notable differences between male and female children warrant further study.
SAN DIEGO — Epigenetic changes — particularly altered DNA methylation — at birth may be associated with risk for metabolic dysfunction later in life, according to research presented at Digestive Disease Week.
Imprinted genes, which are affected by imprint control regions, can be turned on or off with altered DNA methylation and play a key role in development and adult disease, according to study background.
“Imagine being able to screen for metabolic risk the way we screen for hearing or vision — that’s the kind of future this research points toward,” Ashley Jowell, MD, internal medicine resident physician at Duke University, said during her presentation. “What’s exciting is that we now have a tool that can scan the entire genome for these imprint control regions, which is something that wasn’t possible before.”
In the study, Jowell and colleagues used data from the Newborn Epigenetics Study (NEST) cohort, which included children born in North Carolina between 2005 and 2011 and followed through pre-teenage years, to determine whether epigenetic changes at birth predict disease later in life.
The researchers used blood collected from the umbilical cord at birth and evaluated pre-teenage (aged 7-12 years) metabolic health outcomes, including BMI, liver fat measured via protein density fat fraction, blood pressure, cholesterol and waist-to-hip ratio.
They then used an imprintome array (Illumina) to model whether imprint control regions correlated with metabolic dysfunction.
Their focus included more than 1,000 regions of the genome known to be essential in regulating genes during early development, controlling for maternal factors like BMI, smoking and education, Jowell noted.
“We looked at methylation markers, which are small chemical changes in DNA that act like switches, turning genes on or off,” Jowell said. “These switches are usually set during fetal development and can last for life.”
The researchers identified several imprint control regions for which DNA methylation at birth appeared linked to pre-teenage metabolic dysfunction. Moreover, altered methylation on the 16 established regions correlated with metabolic dysfunction.
Among the imprinted genes were:
- TNS3, which is associated with the regulation of liver cancer genes;
- CSMD1, a biomarker of hepatocellular carcinoma prognosis;
- SNHG14|SNRPN|SNURF, which are linked to Prader Willi Syndrome; and
- GNAS, which is associated with obesity and insulin resistance.
Jowell noted that they also observed differences between the sexes in metabolic outcomes.
“In girls, we saw even more connections between certain DNA changes in things like high BMI, blood pressure and liver health,” she said. “In boys, we saw more changes in [alanine aminotransferase]. These sex differences might explain why metabolic disease often shows up differently in boys and girls.”
Jowell and colleagues are conducting a larger follow-up study to validate these results.
“If confirmed in larger studies, these DNA markers could help doctors spot health risks earlier, maybe even at birth,” she said. “That would open the door to helping pediatricians and families take action before problems start.”
For more information:
Ashley Jowell, MD, can be reached at gastroenterology@healio.com.
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Jowell A, et al. Identification of imprint control regions associated with clinically significant metabolic dysfunction in children. Presented at: Digestive Disease Week; May 4-6, 2025; San Diego.