Epigenic markers detected in umbilical cord blood at birth could signify risk for metabolic disease and increased liver fat over the course of a lifespan, according to research presented at Digestive Disease Week 2025.
“If these DNA markers are confirmed in larger studies, they could help doctors spot health risks earlier, maybe even at birth,” said lead author Ashley Jowell, MD, a resident physician in internal medicine at Duke University Health System. “That would open the door to helping families and pediatricians take action before problems start.”
Imprint control regions (ICRs) are areas of a chromosome that are epigenetically modified by parent-of-origin methylation to affect downstream imprinted gene expression. These epigenetic changes continue throughout a person’s life and may play a role in disease risk and pathogenesis.
“Our research looked at whether something in a baby's DNA at birth could help protect preventable health issues later in life,” said Dr. Jowell. “We looked at methylation markers, which are small chemical changes in DNA that act like switches turning genes on or off. These switches are usually set during fetal development and can last for life.”
The goal of their study was to identify ICRs with altered methylation (AM), and the nearest genes, that were associated with clinically significant markers of metabolic dysfunction in children. Dr Jowell and colleagues analyzed umbilical cord blood from 38 children who were enrolled in the Newborn Epigenetics Study, a long-term birth cohort study based in North Carolina. DNA changes in ICRs were assessed using health data that was collected when the children were 7 to 12 years old.
Evaluation for metabolic dysfunction included liver fat content (LFC) that was quantified by MRI, serum triglycerides (TG), blood pressure, body mass index (BMI), and waist and hip circumference. Methylation was quantified in umbilical cord blood, and models were controlled for maternal factors including BMI, education, and smoking status, and also the child’s age. The team then modeled whether imprint control regions were associated with metabolic dysfunction using a Novel Illumina Imprintome Array.
Dr Jowell explained that they analyzed the DNA from birth to see if they could find patterns. “We focused on about 1 ,000 regions of the genome known to be important for regulating genes during early development,” she said. “We found several DNA markers at birth that were linked to health issues later in childhood. One region, called TNS3, was connected to liver fat and body shape, both signs of future risk.”
The most common and significant ICRs with altered methylation were associated with waist hip ratio (WHR) (n=545 ICRs). TNS3 was also associated with diastolic blood pressure (DBP), and they also identified four ICRs corresponding to six genes (ZIM2, PEG3, MIMT1, TCEA1P3, ITPK1, and HSPB1P2) that were significantly associated with various features of metabolic dysfunction in females (n = 23). These include increased child BMI, TG, hip circumference and DBP. An additional ICR, located close to the BEX4 gene, was also associated with increased LFC, DBP, hip circumference, and BMI in girls.
“In boys, we saw more changes with ALT, which is a liver enzyme, and these sex differences might help explain why metabolic disease often show up differently in boys and girls,” she said. “The genes involved are known to affect fat storage, liver function, and even liver cancer, which makes the findings even more compelling.”
Dr. Jowell acknowledges that the study sample size is small, but that the results are consistent with what other researchers have found. A larger National Health Institute-funded follow-up study is currently underway to validate these findings.
“Identification of imprint control regions associated with clinically significant metabolic dysfunction in children.” Abstract 324. Presented May 4, 2025. Digestive Disease Week 2025.
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