title: Epigenetic markers for newborn congenital heart defect (CHD).
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Obstetrics and Gynecology , William Beaumont School of Medicine, Oakland University , Royal Oak , MI , USA and.
authors.forename: Ray O
authors.initials: RO
authors.lastname: Bahado-Singh
authors.affiliation: b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Zaffra
authors.affiliation: b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Samet
authors.initials: S
authors.lastname: Albayarak
authors.affiliation: b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Anushka
authors.initials: A
authors.lastname: Chelliah
authors.affiliation: b Department of Obstetrics and Gynecology , Wayne State University School of Medicine , Detroit , MI , USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bolinjkar
authors.affiliation: a Department of Obstetrics and Gynecology , William Beaumont School of Medicine, Oakland University , Royal Oak , MI , USA and.
authors.forename: Onur
authors.initials: O
authors.lastname: Turkoglu
authors.affiliation: a Department of Obstetrics and Gynecology , William Beaumont School of Medicine, Oakland University , Royal Oak , MI , USA and.
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D063990:Gene Ontology; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn
chemical_list: D015415:Biomarkers
keywords: Epigenetics; heart defect detection