TY - JOUR
T1 - Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human
AU - Wijnands, Kim Pj
AU - Chen, Jun
AU - Liang, Liming
AU - Verbiest, Michael Mpj
AU - Lin, Xihong
AU - Helbing, Willem A.
AU - Gittenberger-De Groot, Adriana C.
AU - Van Der Spek, Peter J.
AU - Uitterlinden, André G.
AU - Steegers-Theunissen, Régine Pm
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Aim: 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. Materials & methods: We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children. Results: 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. Conclusion: These findings provide novel insights in the pathogenesis of perimembranous ventricular septal defect, which is of interest for future prediction and prevention.
AB - Aim: 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. Materials & methods: We examined epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip in 84 case children and 196 control children. Results: 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. Conclusion: These findings provide novel insights in the pathogenesis of perimembranous ventricular septal defect, which is of interest for future prediction and prevention.
KW - bisulfite pyrosequencing
KW - case-control studies
KW - DNA methylation
KW - epigenetics
KW - epigenome-wide
KW - Illumina 450k
KW - perimembranous ventricular septal defects
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U2 - 10.2217/epi-2016-0093
DO - 10.2217/epi-2016-0093
M3 - Article
C2 - 28140654
AN - SCOPUS:85014034830
SN - 1750-1911
VL - 9
SP - 241
EP - 251
JO - Epigenomics
JF - Epigenomics
IS - 3
ER -