TY - JOUR
T1 - Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease
AU - Yuan, Xi
AU - Huang, Jiayu
AU - Wen, Li
AU - Novakovic, Boris
AU - Kilby, Mark D.
AU - Tong, Chao
AU - Qi, Hongbo
AU - Saffery, Richard
AU - Baker, Philip N.
N1 - Sources of funding: This work was supported by the National Natural Science Foundation of China (U21A20346, 82171662, 82101711, 82001580, and 81520108013), Chongqing Science and Technology Commission (cstc2021ycjh-bgzxm0192), Chongqing Health Committee (2019GDRC012), and Chongqing Education Commission (KJZD-K202100404).
PY - 2023/3
Y1 - 2023/3
N2 - Background: Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. Methods: Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. Results: 379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. Conclusions: Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. Trial registration: ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.
AB - Background: Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. Methods: Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. Results: 379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. Conclusions: Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. Trial registration: ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.
KW - Congenital heart disease
KW - DNA methylation
KW - Monozygotic twins
KW - Umbilical cord blood
UR - http://www.scopus.com/inward/record.url?scp=85146939564&partnerID=8YFLogxK
U2 - 10.1016/j.ygeno.2023.110565
DO - 10.1016/j.ygeno.2023.110565
M3 - Article
C2 - 36690264
AN - SCOPUS:85146939564
SN - 0888-7543
VL - 115
JO - Genomics
JF - Genomics
IS - 2
M1 - 110565
ER -