Replicated Umbilical Cord Blood DNA Methylation Loci Associated with Gestational Age at Birth

ABSTRACTBackgroundDNA 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.

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Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth

Epigenetics ◽

10.1080/15592294.2020.1767277 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1243-1258 ◽

Cited By ~ 1

Author(s):

Timothy P. York ◽

Shawn J. Latendresse ◽

Colleen Jackson-Cook ◽

Dana M. Lapato ◽

Sara Moyer ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Gestational Age ◽

Gestational Age At Birth ◽

Age At Birth

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Blood serum myokine irisin and adipocytokine levels in newborns small for gestational age at birth

Proceedings of the National Academy of Sciences of Belarus Medical series ◽

10.29235/1814-6023-2021-18-4-402-412 ◽

2021 ◽

Vol 18 (4) ◽

pp. 402-412

Author(s):

V. A. Prylutskaya ◽

A. V. Sukalo ◽

A. V. Goncharik

Keyword(s):

Blood Serum ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Gestational Age ◽

Small For Gestational Age ◽

The Body ◽

Delivery Mode ◽

Gestational Age At Birth ◽

Age At Birth

In recent years, a number of the studies of myokine irisin in adults and isolated in newborns have been carried out. The role of adipocytokines in the growth and development of the fetus and children has been shown.The aim of the study was to assess the levels of myokine irisin and adipocytokines in newborns small for gestational age at birth and to analyze the relationship between the parameters of the hormonal status of children and their mothers.49 newborns and their mothers were examined. Two groups were identified: group 1 (Gr1) – newborns small for gestational age (n = 24), group 2 (Gr2) – newborns appropriate for gestational age (n = 25). The levels of irisin and adipocytokines in the blood serum were determined by the enzyme immunoassay.Newborns small for gestational age had significantly lower levels of leptin and IGF-1 in the umbilical cord blood compared to children with physical development corresponding to the gestational age. There were no significant differences in the irisin content of cord blood serum in newborn Gr1 compared with Gr2. The presence of significant positive correlations between the level of irisin in the umbilical cord blood of newborns small for gestational age and the body weight at birth was established. In Gr1, a positive relationship was found between the irisin levels of mothers and newborns (r = 0.518, p = 0.028). The differences in the irisin content between the groups were established, taking into account the delivery mode (p = 0.0104).The revealed statistically significant differences in the concentrations of the analyzed metabolic markers in mother–child pairs, their relationship with clinical and anthropometric parameters substantiate the possibility of using irisin and adipocytokines as predictors in predicting the formation of metabolic disorders of infants small for gestational age.

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Abstract 5365: Genome-wide DNA methylation analysis in subsets of precursor B-cells isolated from umbilical cord blood.

10.1158/1538-7445.am2013-5365 ◽

2013 ◽

Author(s):

Md Almamun ◽

Kristen H. Taylor

Keyword(s):

Dna Methylation ◽

B Cells ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Methylation Analysis ◽

Genome Wide ◽

Precursor B Cells ◽

Dna Methylation Analysis

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A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood

10.1101/486498 ◽

2018 ◽

Cited By ~ 3

Author(s):

Charles E. Mordaunt ◽

Bo Y. Park ◽

Kelly M. Bakulski ◽

Jason I. Feinberg ◽

Lisa A. Croen ◽

...

Keyword(s):

Gene Expression ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Meta Analysis ◽

Differentially Expressed ◽

Typically Developing ◽

Blood Gene Expression ◽

Genome Wide ◽

Transcriptional Changes

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the United States. ASD risk is thought to arise from a combination of genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers and treatments. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing (Non-TD) or neurotypical children.MethodsGenome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from umbilical cord blood samples from both the Markers of Autism Risk in Babies--Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. An algorithm-based diagnosis from 36 month assessments categorized the younger sibling as either ASD, typically developing (TD), or not ASD but non-typically developing (Non-TD). 59 ASD, 92 Non-TD, and 120 TD subjects were included and differences were identified in ASD versus TD subjects, with Non-TD versus TD as a specificity control. Meta-analysis was used to combine the results from both studies. Functional enrichments of differentially-expressed genes were examined across diagnostic groups.ResultsWhile cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance when adjusting for multiple comparisons, 172 genes were nominally differentially-expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for toxic substance response and xenobiotic metabolism functions, and gene sets involved in chromatin regulation and systemic lupus erythematosus were significantly upregulated (FDR q < 0.05). In contrast, 66 genes were differentially-expressed between Non-TD and TD cord blood, including only 8 genes that were also differentially-expressed in ASD.ConclusionsThis is the first study to identify perinatal gene expression differences in umbilical cord blood specific to ASD. The results of this meta-analysis across two prospective ASD cohorts support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.

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DNA methylation and brain dysmaturation in preterm infants

10.1101/2021.04.08.21255064 ◽

2021 ◽

Author(s):

Emily N W Wheater ◽

Paola Galdi ◽

Daniel McCartney ◽

Manuel Blesa ◽

Gemma Sullivan ◽

...

Keyword(s):

Dna Methylation ◽

Functional Analysis ◽

Preterm Birth ◽

Brain Development ◽

Gestational Age ◽

Principal Component ◽

Genome Wide ◽

Gestational Age At Birth ◽

Age At Birth ◽

Atypical Brain Development

Preterm birth is associated with dysconnectivity of structural brain networks and is a leading cause of neurocognitive impairment in childhood. Variation in DNA methylation (DNAm) is associated with early exposure to extrauterine life but there has been little research exploring its relationship with brain development. Using genome-wide DNA methylation data from saliva of 258 neonates, we investigated the impact of gestational age on the methylome and performed functional analysis to identify enriched gene sets from probes that contributed to differentially methylated probes (DMPs) or regions (DMRs). We tested the hypothesis that variation in DNAm could underpin the association between preterm birth and atypical brain development by linking DMPs with measures of white matter connectivity derived from diffusion MRI metrics: peak width of skeletonised mean diffusivity (PSMD), fractional anisotropy (PSFA) and neurite density index (PSNDI). Gestational age at birth was associated with widespread differential methylation, with genome-wide significant associations observed for 8,870 CpG probes (p<3.6x10-8) and 1,767 differentially methylated regions. Functional analysis identified 14 enriched gene ontology terms pertaining to cell-cell contacts and cell-extracellular matrix contacts. Principal component analysis of probes with genome-wide significance revealed a first principal component (PC1) that explained 23.5% of variance in DNAm, and this was negatively associated with gestational age at birth. PC1 was associated with PSMD (β=0.349, p=8.37x10-10) and PSNDI (β=0.364, p=4.15x10-5), but not with PSFA (β=-0.035, p=0.510); these relationships mirrored the imaging metrics associations with gestational age at birth. Gestational age at birth has a profound and widely distributed effect on the neonatal saliva methylome. Enriched gene ontology terms related to cell-cell contacts reveal pathways that could mediate the effect of early life environmental exposures on development. Finally, associations between differential DNAm and image markers of white matter tract microstructure suggest that variation in DNAm may provide a link between preterm birth and the dysconnectivity of developing brain networks that characterises atypical brain development in preterm infants.

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Paternal DNA Methylation May Be Associated With Gestational Age at Birth

Epigenetics Insights ◽

10.1177/2516865720930701 ◽

2020 ◽

Vol 13 ◽

pp. 251686572093070

Author(s):

Rui Luo ◽

Nandini Mukherjee ◽

Su Chen ◽

Yu Jiang ◽

S Hasan Arshad ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cell Membrane ◽

Gestational Age ◽

Correlation Coefficients ◽

Functional Enrichment ◽

Cpg Sites ◽

Membrane Adhesion ◽

Gestational Age At Birth ◽

Age At Birth

Background: How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites. Methods: Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC. Results: Analysis of DNAm of fathers collected around their partner’s pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin ( PCDH) gene clusters were associated with gene expression of PCDH in F2 cord blood. Conclusions: Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.

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