ArticlePLoS neglected tropical diseases2021
GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels.
Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 12 citations in OpenAlex.
- DNA Methylation Algorithms of Aging and Incident Cardiovascular Disease: A Prospective Cohort Study.Journal of the American Heart Association · 2025Article
- Associations of DNA Methylation Algorithms of Aging With Cardiovascular Disease and Mortality Risk Among US Older Adults.Journal of the American Heart Association · 2025Article
- Cardiac involvement in Chagas disease and African trypanosomiasis.Nature reviews. Cardiology · 2024Review
- A holistic approach to understanding immune-mediated inflammatory diseases: bioinformatic tools to integrate omics data.Computational and structural biotechnology journal · 2024Review
- Clinical features of Chagas disease progression and severity.Lancet regional health. Americas · 2024Review
- A Systematic Review of Lipid-Focused Cardiovascular Disease Research: Trends and Opportunities.Current issues in molecular biology · 2023Review
- Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.Frontiers in immunology · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
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.
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