Cargando…

The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases

Congenital heart defect (CHD) is a rare and complicated disease with a high mortality rate. Its etiology remains unclear and includes many aspects. DNA methylation has been indicated to be involved in heart development in the early stage of life, and aberrant methylation level was related to CHDs. T...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Jing, Ma, Xiaoqin, Zhang, Qi, Chen, Yinghui, Wu, Dan, Zhao, Pengjun, Yu, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143053/
https://www.ncbi.nlm.nih.gov/pubmed/34041244
http://dx.doi.org/10.3389/fcell.2021.665514
_version_ 1783696675461660672
author Wang, Jing
Ma, Xiaoqin
Zhang, Qi
Chen, Yinghui
Wu, Dan
Zhao, Pengjun
Yu, Yu
author_facet Wang, Jing
Ma, Xiaoqin
Zhang, Qi
Chen, Yinghui
Wu, Dan
Zhao, Pengjun
Yu, Yu
author_sort Wang, Jing
collection PubMed
description Congenital heart defect (CHD) is a rare and complicated disease with a high mortality rate. Its etiology remains unclear and includes many aspects. DNA methylation has been indicated to be involved in heart development in the early stage of life, and aberrant methylation level was related to CHDs. This study provides the first evidence of the cross talk of SNP variants and DNA methylation in clarifying CHD underlying genomic cause. We gathered whole exome sequencing (WES) data for Group 1 consisting of patients with PA (n = 78), TOF (n = 20), TAPVC (n = 78), and PDA (n = 40), and 100 healthy children as control group. Rare non-synonymous mutations and novel genes were found and highlighted. Meanwhile, we carried out the second analysis of DNA methylation data from patients with PA (n = 3), TAPVC (n = 3), TOF (n = 3), and PDA (n = 2), and five healthy controls using 850 K array in Group 2. DNA methylation was linked to WES data, and we explored an obvious overlap of hyper/hypomethylated genes. Next, we identified some candidate genes by Fisher’s exact test and Burden analysis; then, those methylated genes were figured out by the criteria of the mutation located in the CpG islands of the genome, differential methylation sites (DMS), and DNA methylation quantitative trait loci (meQTLs) in the database, respectively. Also, the interaction of differentially methylated candidate genes with known CHD pathogenetic genes was depicted in a molecular network. Taken together, our findings show that nine novel genes (ANGPTL4, VEGFA, PAX3, MUC4, HLA-DRB1, TJP2, BCR, PKD1, and HK2) in methylation level are critical to CHD and reveal a new insight into the molecular pathogenesis of CHD.
format Online
Article
Text
id pubmed-8143053
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81430532021-05-25 The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases Wang, Jing Ma, Xiaoqin Zhang, Qi Chen, Yinghui Wu, Dan Zhao, Pengjun Yu, Yu Front Cell Dev Biol Cell and Developmental Biology Congenital heart defect (CHD) is a rare and complicated disease with a high mortality rate. Its etiology remains unclear and includes many aspects. DNA methylation has been indicated to be involved in heart development in the early stage of life, and aberrant methylation level was related to CHDs. This study provides the first evidence of the cross talk of SNP variants and DNA methylation in clarifying CHD underlying genomic cause. We gathered whole exome sequencing (WES) data for Group 1 consisting of patients with PA (n = 78), TOF (n = 20), TAPVC (n = 78), and PDA (n = 40), and 100 healthy children as control group. Rare non-synonymous mutations and novel genes were found and highlighted. Meanwhile, we carried out the second analysis of DNA methylation data from patients with PA (n = 3), TAPVC (n = 3), TOF (n = 3), and PDA (n = 2), and five healthy controls using 850 K array in Group 2. DNA methylation was linked to WES data, and we explored an obvious overlap of hyper/hypomethylated genes. Next, we identified some candidate genes by Fisher’s exact test and Burden analysis; then, those methylated genes were figured out by the criteria of the mutation located in the CpG islands of the genome, differential methylation sites (DMS), and DNA methylation quantitative trait loci (meQTLs) in the database, respectively. Also, the interaction of differentially methylated candidate genes with known CHD pathogenetic genes was depicted in a molecular network. Taken together, our findings show that nine novel genes (ANGPTL4, VEGFA, PAX3, MUC4, HLA-DRB1, TJP2, BCR, PKD1, and HK2) in methylation level are critical to CHD and reveal a new insight into the molecular pathogenesis of CHD. Frontiers Media S.A. 2021-05-04 /pmc/articles/PMC8143053/ /pubmed/34041244 http://dx.doi.org/10.3389/fcell.2021.665514 Text en Copyright © 2021 Wang, Ma, Zhang, Chen, Wu, Zhao and Yu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wang, Jing
Ma, Xiaoqin
Zhang, Qi
Chen, Yinghui
Wu, Dan
Zhao, Pengjun
Yu, Yu
The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
title The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
title_full The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
title_fullStr The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
title_full_unstemmed The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
title_short The Interaction Analysis of SNP Variants and DNA Methylation Identifies Novel Methylated Pathogenesis Genes in Congenital Heart Diseases
title_sort interaction analysis of snp variants and dna methylation identifies novel methylated pathogenesis genes in congenital heart diseases
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143053/
https://www.ncbi.nlm.nih.gov/pubmed/34041244
http://dx.doi.org/10.3389/fcell.2021.665514
work_keys_str_mv AT wangjing theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT maxiaoqin theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT zhangqi theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT chenyinghui theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT wudan theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT zhaopengjun theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT yuyu theinteractionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT wangjing interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT maxiaoqin interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT zhangqi interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT chenyinghui interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT wudan interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT zhaopengjun interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases
AT yuyu interactionanalysisofsnpvariantsanddnamethylationidentifiesnovelmethylatedpathogenesisgenesincongenitalheartdiseases