Epigenetic markers for newborn congenital heart defect (CHD).

OBJECTIVE

Our objective was to determine whether there were significant differences in genome-wide DNA methylation in newborns with major congenital heart defect (CHD) compared to controls. We also evaluated methylation of cytosines in CpG motifs for the detection of these CHDs.

METHODS

Genome-wide DNA methylation analysis was performed on DNA from 60 newborns with various CHDs, including hypoplastic left heart syndrome, ventricular septal deficit, atrial septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of Fallot, and 32 controls.

RESULTS

Highly significant differences in cytosine methylation were seen in a large number of genes throughout the genome for all CHD categories. Gene ontology analysis of CHD overall indicated over-represented biological processes involving cell development and differentiation, and anatomical structure morphogenesis. Methylation of individual cytosines in CpG motifs had high diagnostic accuracy for the detection of CHD. For example, for coarctation one predictive model based on levels of particular cytosine nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974, p < 0.00001).

CONCLUSION

Profound differences in cytosine methylation were observed in hundreds of genes in newborns with different types of CHD. There appears to be the potential for development of accurate genetic biomarkers for CHD detection in newborns.