Ticking of DNA methylation clocks tied to higher odds of asthma and atopy in children
Known as the atopic or allergic march, it’s a familiar progression to pediatricians and parents alike: atopic dermatitis and food allergies emerge in infancy or early childhood, followed by rhinitis and asthma as the child gets older. But what if it were possible to stop this march in its tracks? A new study in Project Viva by investigators at Brigham and Women’s Hospital looks beyond genetics to the realm of epigenetics — in this case a DNA modification that influences what sections of the genetic code are read out — for clues about asthma and allergies in childhood. Project Viva is a groundbreaking cohort study focused on characterizing early life factors that influence long-term health. Researchers at Harvard Pilgrim Health Care Institute and colleagues have followed Boston-area mothers and children enrolled in Project Viva for almost two decades. Using data from Project Viva, the investigative team evaluated the association between molecular markers of epigenetic changes and the occurrence of allergy and asthma to find a connection to accelerated DNA methylation age. The team’s results are published in The Journal of Allergy & Clinical Immunology.
“We know that the prevalence of allergies and asthma has been increasing over the past decade. The genome hasn’t changed, but some of the ways that the environment is interacting with our genomes may have,” said senior author Dawn DeMeo, MD, MPH, a pulmonary/critical care specialist and senior respiratory genetics researcher in the Channing Division of Network Medicine at the Brigham. “We wanted to explore if these mechanisms can be captured or measured by examining the epigenome. If so, we may have a way of better understanding early susceptibility to asthma and allergies and what exposures may be influencing the emergence of disease.”
As part of Project Viva, investigators collected blood samples from children at the time of birth (umbilical cord blood), in early childhood and then in mid-childhood. For this study, DNA was extracted from these samples and DNA methylation data was collected. Methylation represents a chemical change that can activate or repress a segment of DNA without altering the DNA sequence.
To understand how changes across the epigenome might correlate with allergies and asthma, the team used “epigenetic clocks” to measure how much DNA methylation was occurring in each participant. As humans age, methylation naturally changes over time. These changes can be aggregated to capture the idea of biologic age or an “epigenetic clock.” In some individuals, the epigenetic clock appears to be ticking faster — a phenomenon referred to as accelerated DNA methylation age (DNAmAge). Previous research has focused on DNAmAge in adult diseases, including physical and cognitive decline, Parkinson’s disease and lung cancer, but it has not previously been studied in childhood asthma or allergy.
The team found that by mid-childhood, accelerated DNAmAge was associated with higher levels of IgE (antibodies typically found in the blood of people with allergies) and greater odds of atopic sensitization, environmental allergies, food allergies and asthma. The team replicated their findings in a collection of samples from children in Costa Rica.
“We believe that there are early environmental exposures that push toward the appearance of accelerated epigenetic age, since we’re seeing this association by mid-childhood,” said DeMeo.
“There’s are likely environmental exposures and DNA changes that are occurring in this window of time that do not seem to be apparent at birth. If we can target our future investigations on early exposures such as nutrition, we may be able to use epigenetic clocks to find out what changes we can make to modify this trajectory toward the development of asthma and allergy.”
The authors note that the association between DNAmAge and allergies/asthma is correlative, and from the data alone it cannot be determined if the epigenetic changes are causing increased risk of allergic conditions or vice versa. In addition, the epigenetic clocks used in this study were optimized for adults, not for children. The research team hopes to further refine its epigenetic investigations by studying larger cohorts of children with epigenetic clocks optimized for younger individuals.
The Project Viva study is supported by grants from the National Institutes of Health (NIH R01 HL 111108, P01 HL 132825, R01 NR013945, R01 HD 034568, UH3OD023286, K23 ES022242, R01 AI102960).
BRIGHAM AND WOMEN’S HOSPITAL