title: Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human.
abstract: Congenital heart diseases are the most common birth defects worldwide and leading cause of infant mortality. The perimembranous ventricular septal defect is most prevalent. Epigenetics may provide an underlying mechanism of the gene-environment interactions involved.
  
  
  
  We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children.
  
  
  
  We identified differential methylation of a CpG locus (cg17001566) within the PRDM16 gene after Bonferroni correction (p = 9.17 × 10-8). This was validated by bisulfite pyrosequencing. PRDM16 functions as a repressor of TGF-β signaling controlling tissue morphogenesis crucial during cardiogenesis. At 15% false-discovery rate, we identified seven additional CpG loci.
  
  
  
  These findings provide novel insights in the pathogenesis of perimembranous ventricular septal defect, which is of interest for future prediction and prevention.
authors.affiliation: Department of Obstetrics & Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Kim Pj
authors.initials: KP
authors.lastname: Wijnands
authors.affiliation: Division of Biomedical Statistics & Informatics & Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Michael Mpj
authors.initials: MM
authors.lastname: Verbiest
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Paediatrics, Division of Paediatric Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Helbing
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.affiliation: Department of Bioinformatics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Obstetrics & Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Régine Pm
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000592:standards; D006345:Heart Septal Defects, Ventricular / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C416371:PRDM16 protein, human; D014157:Transcription Factors
keywords: DNA methylation; Illumina 450k; bisulfite pyrosequencing; case–control studies; epigenetics; epigenome-wide; perimembranous ventricular septal defects