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Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease

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journal contribution
posted on 2024-03-26, 14:28 authored by Xi Yuan, Jiayu Huang, Li Wen, Boris Novakovic, Mark D Kilby, Chao Tong, Hongbo Qi, Richard Saffery, Philip N Baker

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.

History

Author affiliation

College of Life Sciences

Version

  • VoR (Version of Record)

Published in

Genomics

Volume

115

Issue

2

Pagination

110565

Publisher

Elsevier BV

issn

0888-7543

eissn

1089-8646

Copyright date

2023

Available date

2024-03-26

Spatial coverage

United States

Language

en

Deposited by

Professor Philip Baker

Deposit date

2024-03-26

Rights Retention Statement

  • No

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