Using Residual Newborn Blood Spots to Investigate CpG Methylation in Relation to Air Pollution and Congenital Heart...

The prevalence of tetralogy of Fallot (TOF), a common congenital heart defect, has increased over the last two decades.

Genome-wide CpG methylation patterns were assessed and analyzed in relation to gestational air pollution exposure among 24 infants with TOF and 24 sex-matched control infants without a birth defect from a North Carolina population-based, case-control study of major structural birth defects (2006-2011). Air pollution exposure during obstetric weeks 3-8 was assigned based on self-reported residence. DNA was extracted from residual newborn blood spots, and DNA methylation levels were measured using the Illumina EPIC Array.

Cases had higher exposure to both PM_{2 .5} and O₃ compared to controls. No specific CpG loci were statistically significantly associated with TOF status or air pollution exposure; however, we observed associations between TOF case status and DNA methylation at specific genomic regions with genes enriched for functions in metabolism. Additionally, there were significant regions that displayed differential DNA methylation in relation to air pollution exposure within genes involved in apoptosis, necrosis, inflammation, and immune response pathways.

Generally, air pollution exposure and TOF were associated with differential DNA methylation in distinct genes. These results highlight suggestive links between the environment, epigenome, and TOF to be further investigated in larger studies.