GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels.
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 polymor...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0009874 |
| _version_ | 1819282975275089920 |
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| author | Desiré Casares-Marfil Martin Kerick Eduardo Andrés-León Pau Bosch-Nicolau Israel Molina Chagas Genetics CYTED Network Javier Martin Marialbert Acosta-Herrera |
| author_facet | Desiré Casares-Marfil Martin Kerick Eduardo Andrés-León Pau Bosch-Nicolau Israel Molina Chagas Genetics CYTED Network Javier Martin Marialbert Acosta-Herrera |
| author_sort | Desiré Casares-Marfil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T01:24:07Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-24T01:24:07Z |
| publishDate | 2021-10-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-bd5a6ba8264443278c16932d615527a52022-12-21T17:22:34ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352021-10-011510e000987410.1371/journal.pntd.0009874GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels.Desiré Casares-MarfilMartin KerickEduardo Andrés-LeónPau Bosch-NicolauIsrael MolinaChagas Genetics CYTED NetworkJavier MartinMarialbert Acosta-HerreraA 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.https://doi.org/10.1371/journal.pntd.0009874 |
| spellingShingle | Desiré Casares-Marfil Martin Kerick Eduardo Andrés-León Pau Bosch-Nicolau Israel Molina Chagas Genetics CYTED Network Javier Martin Marialbert Acosta-Herrera GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels. PLoS Neglected Tropical Diseases |
| title | GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels. |
| title_full | GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels. |
| title_fullStr | GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels. |
| title_full_unstemmed | GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels. |
| title_short | GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels. |
| title_sort | gwas loci associated with chagas cardiomyopathy influences dna methylation levels |
| url | https://doi.org/10.1371/journal.pntd.0009874 |
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