Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human

Kim Pj Wijnands, Jun Chen, Liming Liang, Michael Mpj Verbiest, Xihong Lin, Willem A. Helbing, Adriana C. Gittenberger-De Groot, Peter J. Van Der Spek, André G. Uitterlinden, Régine Pm Steegers-Theunissen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)241-251
Number of pages11
JournalEpigenomics
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Ventricular Heart Septal Defects
Methylation
Genome
Gene-Environment Interaction
Infant Mortality
DNA Methylation
Morphogenesis
Epigenomics
Heart Diseases
Genes
hydrogen sulfite

Keywords

  • bisulfite pyrosequencing
  • case-control studies
  • DNA methylation
  • epigenetics
  • epigenome-wide
  • Illumina 450k
  • perimembranous ventricular septal defects

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Wijnands, K. P., Chen, J., Liang, L., Verbiest, M. M., Lin, X., Helbing, W. A., ... Steegers-Theunissen, R. P. (2017). Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human. Epigenomics, 9(3), 241-251. https://doi.org/10.2217/epi-2016-0093

Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human. / Wijnands, Kim Pj; Chen, Jun; Liang, Liming; Verbiest, Michael Mpj; Lin, Xihong; Helbing, Willem A.; Gittenberger-De Groot, Adriana C.; Van Der Spek, Peter J.; Uitterlinden, André G.; Steegers-Theunissen, Régine Pm.

In: Epigenomics, Vol. 9, No. 3, 01.03.2017, p. 241-251.

Research output: Contribution to journalArticle

Wijnands, KP, Chen, J, Liang, L, Verbiest, MM, Lin, X, Helbing, WA, Gittenberger-De Groot, AC, Van Der Spek, PJ, Uitterlinden, AG & Steegers-Theunissen, RP 2017, 'Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human', Epigenomics, vol. 9, no. 3, pp. 241-251. https://doi.org/10.2217/epi-2016-0093
Wijnands, Kim Pj ; Chen, Jun ; Liang, Liming ; Verbiest, Michael Mpj ; Lin, Xihong ; Helbing, Willem A. ; Gittenberger-De Groot, Adriana C. ; Van Der Spek, Peter J. ; Uitterlinden, André G. ; Steegers-Theunissen, Régine Pm. / Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human. In: Epigenomics. 2017 ; Vol. 9, No. 3. pp. 241-251.
@article{f3f9c28c9ff64c22befe5c982d78cc31,
title = "Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human",
abstract = "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.",
keywords = "bisulfite pyrosequencing, case-control studies, DNA methylation, epigenetics, epigenome-wide, Illumina 450k, perimembranous ventricular septal defects",
author = "Wijnands, {Kim Pj} and Jun Chen and Liming Liang and Verbiest, {Michael Mpj} and Xihong Lin and Helbing, {Willem A.} and {Gittenberger-De Groot}, {Adriana C.} and {Van Der Spek}, {Peter J.} and Uitterlinden, {Andr{\'e} G.} and Steegers-Theunissen, {R{\'e}gine Pm}",
year = "2017",
month = "3",
day = "1",
doi = "10.2217/epi-2016-0093",
language = "English (US)",
volume = "9",
pages = "241--251",
journal = "Epigenomics",
issn = "1750-1911",
publisher = "Future Medicine Ltd.",
number = "3",

}

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

UR - http://www.scopus.com/inward/record.url?scp=85014034830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014034830&partnerID=8YFLogxK

U2 - 10.2217/epi-2016-0093

DO - 10.2217/epi-2016-0093

M3 - Article

VL - 9

SP - 241

EP - 251

JO - Epigenomics

JF - Epigenomics

SN - 1750-1911

IS - 3

ER -