In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 10 ( 2021-10-29), p. e0009874-
Abstract:
A recent genome-wide association study (GWAS) identified a locus in chromosome 11 associated with the chronic cardiac form of Chagas disease. Here we aimed to elucidate the potential functional mechanism underlying this genetic association by analyzing the correlation among single nucleotide polymorphisms (SNPs) and DNA methylation (DNAm) levels as cis methylation quantitative trait loci ( cis -mQTL) within this region. A total of 2,611 SNPs were tested against 2,647 DNAm sites, in a subset of 37 chronic Chagas cardiomyopathy patients and 20 asymptomatic individuals from the GWAS. We identified 6,958 significant cis -mQTLs (False Discovery Rate [FDR] 〈 0.05) at 1 Mb each side of the GWAS leading variant, where six of them potentially modulate the expression of the SAC3D1 gene, the reported gene in the previous GWAS. In addition, a total of 268 cis -mQTLs showed differential methylation between chronic Chagas cardiomyopathy patients and asymptomatic individuals. The most significant cis -mQTLs mapped in the gene bodies of POLA2 (FDR = 1.04x10 -11 ), PLAAT3 (FDR = 7.22x10 -03 ), and CCDC88B (FDR = 1.89x10 -02 ) that have been associated with cardiovascular and hematological traits in previous studies. One of the most relevant interactions correlated with hypermethylation of CCDC88B . This gene is involved in the inflammatory response, and its methylation and expression levels have been previously reported in Chagas cardiomyopathy. Our findings support the functional relevance of the previously associated genomic region, highlighting the regulation of novel genes that could play a role in the chronic cardiac form of the disease.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009874
DOI:
10.1371/journal.pntd.0009874.g001
DOI:
10.1371/journal.pntd.0009874.g002
DOI:
10.1371/journal.pntd.0009874.t001
DOI:
10.1371/journal.pntd.0009874.t002
DOI:
10.1371/journal.pntd.0009874.s001
DOI:
10.1371/journal.pntd.0009874.s002
DOI:
10.1371/journal.pntd.0009874.s003
DOI:
10.1371/journal.pntd.0009874.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
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