Persistent DNA methylation changes associated with prenatal NO₂exposure in a Canadian prospective birth study

Abstract

BackgroundAccumulating evidence suggests prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. However, it remains unclear whether prenatal DNAm alterations persist through early life. Identifying DNAm changes that persist from birth into childhood would provide greater insight into the molecular mechanisms that most likely contribute to the association of prenatal air pollution exposure with health outcomes such as atopic disease.ObjectivesThis study investigated the persistence of DNAm changes associated with prenatal NO2exposure (a surrogate measure of traffic-related air pollution) at age one to begin characterizing which DNAm changes most likely to contribute to atopic disease.MethodsWe used an atopy-enriched subset of CHILD study participants (N=145) to identify individual and regional cord blood DNAm differences associated with prenatal NO2, followed by an investigation of persistence in age one peripheral blood. As we had repeated DNAm measures, we also isolated postnatal-specific DNAm changes and examined their association with NO2exposure in the first year of life. MANOVA tests were used to examine the association between DNAm changes associated with NO2and child wheeze and atopy.ResultsWe identified 24 regions of altered cord blood DNAm, with several annotated toHOXgenes. Two regions annotated toMPDU1andC5orf63were significantly associated with age one wheeze. Further, we found the effect of prenatal NO2exposure across CpGs within all altered regions remained similar at age one. A single region of postnatal-specific DNAm annotated toHOXB6was associated with year one NO2and age one atopy.DiscussionRegional cord blood DNAm changes associated with prenatal NO2exposure persist through at least the first year of life, and some of these changes are associated with age one wheeze. The early-postnatal period remains a sensitive window to DNAm perturbations that may also influence child health.