scholarly journals Replication of DNA Methylation Variation Reported in Cord Blood Samples From GDM-Affected Pregnancies in Preadolescent and Adolescent Offspring of Women With GDM

Diabetes Care ◽  
2021 ◽  
pp. dc210248
Author(s):  
Line Hjort ◽  
Louise Groth Grunnet ◽  
Richard Saffery ◽  
Sjurdur Olsen ◽  
Allan Vaag
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Blood Samples ◽  
Adolescent Offspring ◽  
Methylation Variation

scholarly journals Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

2017 ◽  
Author(s):  
John Dou ◽  
Rebecca J. Schmidt ◽  
Kelly S. Benke ◽  
Craig Newschaffer ◽  
Irva Hertz-Picciotto ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cell ◽  
Cord Blood ◽  
Whole Blood ◽  
Cell Types ◽  
Buffy Coat ◽  
Sample Type ◽  
Blood Samples ◽  
Cell Composition ◽  
Cell Counts

AbstractBackgroundCord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells by generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability.ObjectivesTo evaluate differences in cell composition and DNA methylation between buffy coat and whole cord blood samples.MethodsCord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in 8 individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition.ResultsDNA methylation PCs were associated with individual (PPC1=1.4x10-9; PPC2=2.9x10-5; PPC3=3.8x10-5; PPC4=4.2x10-6; PPC5=9.9x10-13), and not with sample type (PPC1-5>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired individual samples ranged from r=0.66 to r=0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (5 sites had unadjusted P<10-5). Estimated cell type proportions did not differ by sample type (P=0.86), and estimated cell counts were highly correlated between paired samples (r=0.99).ConclusionsDifferences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

scholarly journals Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring

2015 ◽  
Vol 24 (11) ◽  
pp. 3021-3029 ◽  
Author(s):  
Sarah Finer ◽  
Chris Mathews ◽  
Rob Lowe ◽  
Melissa Smart ◽  
Sara Hillman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gestational Diabetes ◽  
Cord Blood ◽  
Genome Wide ◽  
Methylation Variation

scholarly journals DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

2020 ◽  
Author(s):  
Jenny van Dongen ◽  
Fiona A. Hagenbeek ◽  
Matthew Suderman ◽  
Peter Roetman ◽  
Karen Sugden ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Aggressive Behavior ◽  
Peripheral Blood ◽  
Association Studies ◽  
Meta Analysis ◽  
Risk Tolerance ◽  
Blood Samples ◽  
Chemical Exposures ◽  
Starting Point

AbstractDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2×10−7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

scholarly journals The effect of paternal methyl-group donor intake on offspring DNA methylation and birth weight

2017 ◽  
Vol 8 (3) ◽  
pp. 311-321 ◽  
Author(s):  
S. Pauwels ◽  
I. Truijen ◽  
M. Ghosh ◽  
R. C. Duca ◽  
S. A. S. Langie ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Cord Blood ◽  
Gestational Age ◽  
Methylation Status ◽  
Positive Association ◽  
Blood Samples ◽  
Dna Hydroxymethylation ◽  
Methyl Group ◽  
Nutritional Studies

Most nutritional studies on the development of children focus on mother–infant interactions. Maternal nutrition is critically involved in the growth and development of the fetus, but what about the father? The aim is to investigate the effects of paternal methyl-group donor intake (methionine, folate, betaine, choline) on paternal and offspring global DNA (hydroxy)methylation, offspringIGF2DMR DNA methylation, and birth weight. Questionnaires, 7-day estimated dietary records, whole blood samples, and anthropometric measurements from 74 fathers were obtained. A total of 51 cord blood samples were collected and birth weight was obtained. DNA methylation status was measured using liquid chromatography-tandem mass spectrometry (global DNA (hydroxy)methylation) and pyrosequencing (IGF2DMR methylation). Paternal betaine intake was positively associated with paternal global DNA hydroxymethylation (0.028% per 100 mg betaine increase, 95% CI: 0.003, 0.053,P=0.03) and cord blood global DNA methylation (0.679% per 100 mg betaine increase, 95% CI: 0.057, 1.302,P=0.03). Paternal methionine intake was positively associated with CpG1 (0.336% per 100 mg methionine increase, 95% CI: 0.103, 0.569,P=0.006), and mean CpG (0.201% per 100 mg methionine increase, 95% CI: 0.001, 0.402,P=0.049) methylation of theIGF2DMR in cord blood. Further, a negative association between birth weight/birth weight-for-gestational agez-score and paternal betaine/methionine intake was found. In addition, a positive association between choline and birth weight/birth weight-for-gestational agez-score was also observed. Our data indicate a potential impact of paternal methyl-group donor intake on paternal global DNA hydroxymethylation, offspring global andIGF2DMR DNA methylation, and prenatal growth.

scholarly journals Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan

2021 ◽  
Vol 18 (11) ◽  
pp. 6144
Author(s):  
Yu-Fang Huang ◽  
Chia-Huang Chang ◽  
Pei-Jung Chen ◽  
I-Hsuan Lin ◽  
Yen-An Tsai ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Bisphenol A ◽  
Cord Blood ◽  
Developmental Disorders ◽  
Metabolic Diseases ◽  
System Development ◽  
Maternal Blood ◽  
Blood Samples

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

scholarly journals Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yoshikazu Arai ◽  
Koji Hayakawa ◽  
Daisuke Arai ◽  
Rie Ito ◽  
Yusuke Iwasaki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Cord Blood ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Methylation Status ◽  
Combined Exposure ◽  
Blood Samples ◽  
Low Concentrations ◽  
Induced Pluripotent

The regulation of transcription and genome stability by epigenetic systems are crucial for the proper development of mammalian embryos. Chemicals that disturb epigenetic systems are termed epimutagens. We previously performed chemical screening that focused on heterochromatin formation and DNA methylation status in mouse embryonic stem cells and identified five epimutagens: diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se), and octachlorodipropyl ether (S-421). Here, we used human induced pluripotent stem cells (hiPSCs) to confirm the effects of 20 chemicals, including the five epimutagens, detected at low concentrations in maternal peripheral and cord blood samples. Of note, these individual chemicals did not exhibit epimutagenic activity in hiPSCs. However, because the fetal environment contains various chemicals, we evaluated the effects of combined exposure to chemicals (DEP, Hg, cotinine, Se, and S-421) on hiPSCs. The combined exposure caused a decrease in the number of heterochromatin signals and aberrant DNA methylation status at multiple gene loci in hiPSCs. The combined exposure also affected embryoid body formation and neural differentiation from hiPSCs. Therefore, DEP, Hg, cotinine, Se, and S-421 were defined as an “epimutagen combination” that is effective at low concentrations as detected in maternal peripheral and cord blood.

scholarly journals DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

2021 ◽  
Author(s):  
Jenny van Dongen ◽  
◽  
Fiona A. Hagenbeek ◽  
Matthew Suderman ◽  
Peter J. Roetman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Aggressive Behavior ◽  
Peripheral Blood ◽  
Association Studies ◽  
Meta Analysis ◽  
Risk Tolerance ◽  
Blood Samples ◽  
Chemical Exposures ◽  
Starting Point

AbstractDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

scholarly journals Association of Methylation-Related Nutrient Intake and Status with Offspring DNA Methylation in Pregnant Women with and Without Gestational Diabetes Mellitus

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1016-1016
Author(s):  
Xinyin Jiang ◽  
Chauntelle Jack-Roberts ◽  
Kaydine Edwards ◽  
Ella Gilboa ◽  
Ikhtiyor Djuraev ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dna Methylation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Cord Blood ◽  
Pregnant Women ◽  
Nutrient Intake ◽  
Blood Levels ◽  
Global Dna Methylation ◽  
Blood Samples

Abstract Objectives Gestational diabetes mellitus (GDM) is associated with alterations in DNA methylation in the placenta and offspring tissues. Nutrients participating in the methionine cycle (e.g., choline, betaine, folate, vitamin B12, methionine) influence the supply of methyl groups. The objective of this research was to determine whether maternal intake and status of these nutrients during pregnancy may interact with the GDM status to shape the offspring epigenome. Methods We conducted 3-day dietary recalls and collected blood samples from pregnant women with and without GDM (n = 22/group) to quantify methylation-related nutrient intakes and status. At delivery, we collected cord blood samples and measured global DNA methylation. Results GDM was associated with a 25% increase (P = 0.041) in global DNA methylation in the cord blood. Maternal choline intake (r = −0.602, P = 0.006) as well as cord blood methionine (r = −0.553, P = 0.014) and betaine (r = −0.566, P = 0.011) levels were negatively correlated with cord blood DNA methylation only in non-GDM women, while intakes and maternal blood levels of other methylation-related nutrients were not related to cord blood DNA methylation. Conclusions GDM and methyl nutrient intake/status interact to modify offspring DNA methylation in humans. Funding Sources Egg Nutrition Center.

scholarly journals Genome-wide DNA methylation associations with spontaneous preterm birth in US blacks: findings in maternal and cord blood samples

Epigenetics ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Xiumei Hong ◽  
Ben Sherwood ◽  
Christine Ladd-Acosta ◽  
Shouneng Peng ◽  
Hongkai Ji ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preterm Birth ◽  
Cord Blood ◽  
Spontaneous Preterm Birth ◽  
Blood Samples ◽  
Genome Wide

Genome-wide DNA methylation variation in maternal and cord blood of gestational diabetes population

2017 ◽  
Vol 132 ◽  
pp. 127-136 ◽  
Author(s):  
Jessica Kang ◽  
Chien-Nan Lee ◽  
Hung-Yuan Li ◽  
Kai-Han Hsu ◽  
Shin-Yu Lin
Keyword(s):  
Dna Methylation ◽  
Gestational Diabetes ◽  
Cord Blood ◽  
Genome Wide ◽  
Methylation Variation
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