ArticleHuman genomics2023
Epigenomic signature of major congenital heart defects in newborns with Down syndrome.
Article in Human genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Increased methylation levels of theEpigenomics · 2025Article
- Genome-Wide Association Studies of Down Syndrome Associated Congenital Heart Defects Suggests a Genetically Heterogeneous Risk for CHD in DS.Genetic epidemiology · 2025Article
- Review
- DNA methylation biomarkers of intellectual/developmental disability across the lifespan.Journal of neurodevelopmental disorders · 2025Review
- Infantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.Children (Basel, Switzerland) · 2024Review
- Methods in DNA methylation array dataset analysis: A review.Computational and structural biotechnology journal · 2024Review
- Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.bioRxiv : the preprint server for biology · 2024Article
- Bioinformatics in Neonatal/Pediatric Medicine-A Literature Review.Journal of personalized medicine · 2024Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCongenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs.
methodsWe used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: (1) 45 DS-CHD (27 female, 18 male) and (2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD versus DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell-type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS versus typical development (TD) WGBS NDBS samples.
resultsWe found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percentage of CHD-associated DMRs than background regions were differentially methylated in DS versus TD samples.
conclusionsA sex-specific signature of DNA methylation was detected in NDBS of DS-CHD compared to DS non-CHD individuals. This supports the hypothesis that epigenetics can reflect the variability of phenotypes in DS, particularly CHDs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.