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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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 |
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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 |
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