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

Xi Yuan; Jiayu Huang; Li Wen; Boris Novakovic; Mark Kilby; Chao Tong; Hongbo Qi; Richard Saffery; Phillip N. Baker

doi:10.1016/j.ygeno.2023.110565

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

Xi Yuan, Jiayu Huang, Li Wen, Boris Novakovic, Mark Kilby, Chao Tong, Hongbo Qi^*, Richard Saffery^*, Phillip N. Baker^*

^*Corresponding author for this work

Metabolism and Systems Science

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	110565
Journal	Genomics
Volume	115
Issue number	2
Early online date	20 Jan 2023
DOIs	https://doi.org/10.1016/j.ygeno.2023.110565
Publication status	Published - Mar 2023

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@article{509ae310721e4f4088fd1251fabde25d,

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

abstract = "BackgroundDespite 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.MethodsCord 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.Results379 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.ConclusionsSpecific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD.Trial registrationChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.",

author = "Xi Yuan and Jiayu Huang and Li Wen and Boris Novakovic and Mark Kilby and Chao Tong and Hongbo Qi and Richard Saffery and Baker, {Phillip N.}",

year = "2023",

month = mar,

doi = "10.1016/j.ygeno.2023.110565",

language = "English",

volume = "115",

journal = "Genomics",

issn = "0888-7543",

publisher = "Elsevier",

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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

AU - Tong, Chao

AU - Qi, Hongbo

AU - Saffery, Richard

AU - Baker, Phillip N.

PY - 2023/3

Y1 - 2023/3

N2 - BackgroundDespite 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.MethodsCord 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.Results379 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.ConclusionsSpecific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD.Trial registrationChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.

AB - BackgroundDespite 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.MethodsCord 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.Results379 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.ConclusionsSpecific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD.Trial registrationChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.

U2 - 10.1016/j.ygeno.2023.110565

DO - 10.1016/j.ygeno.2023.110565

M3 - Article

SN - 0888-7543

VL - 115

JO - Genomics

JF - Genomics

IS - 2

M1 - 110565

ER -

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

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