Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth
| Autor: | Aaron R. Wolen, Timothy P. York, Catherine Hoyo, Elizabeth K. Do, Susan K. Murphy, Shawn J. Latendresse, Colleen Jackson-Cook, Sara Moyer, Dana M. Lapato, Jerome F. Strauss, Roxann Roberson-Nay, Bernard F. Fuemmeler |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research Microarray Gestational Age Biology Umbilical cord Andrology Epigenome 03 medical and health sciences 0302 clinical medicine Gene expression medicine Humans Epigenetics Molecular Biology reproductive and urinary physiology 030304 developmental biology Genetics Regulation of gene expression 0303 health sciences Fetus Innate immune system Embryogenesis Infant Newborn dNaM Gestational age Methylation DNA Methylation Fetal Blood Immunity Innate 030104 developmental biology medicine.anatomical_structure CpG site Genetic Loci In utero 030220 oncology & carcinogenesis DNA methylation Premature Birth CpG Islands Female Infant Premature Genome-Wide Association Study Research Paper |
| Zdroj: | Epigenetics |
| ISSN: | 1559-2308 1559-2294 |
| DOI: | 10.1080/15592294.2020.1767277 |
| Popis: | BackgroundDNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The fetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behavior of individual genes.ObjectivesThe aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in matched specimens.ResultsGenome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450K BeadChip, was associated with GA for 2,372 CpG probes (5% false discovery rate) in both the Pregnancy, Race, Environment, Genes (PREG – Virginia Commonwealth University) and Newborn Epigenetic Study (NEST – Duke University) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. This assessment provides a strong evidence to support the importance of DNAm change throughout the gestational time period.ConclusionsThese results converge on support for the role of variation in DNAm measures as an important genetic regulatory mechanism contributing to inter-individual differences in gestational age at birth. In particular, the pathways described are consistent with the well-known hypothesis of pathogen detection and response by the immune system to elicit premature labor as a consequence of unscheduled inflammation. |
| Databáze: | OpenAIRE |
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