Dataset Information

Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs.

ABSTRACT: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array.Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods.Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.

SUBMITTER: Morin AM

PROVIDER: S-EPMC5526324 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs.

Morin Alexander M AM Gatev Evan E McEwen Lisa M LM MacIsaac Julia L JL Lin David T S DTS Koen Nastassja N Czamara Darina D Räikkönen Katri K Zar Heather J HJ Koenen Karestan K Stein Dan J DJ Kobor Michael S MS Jones Meaghan J MJ

Clinical epigenetics 20170725

<h4>Background</h4>Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we use ...[more]

PMID: 28770015

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Project description:BackgroundEpigenetic mechanisms may underlie associations between maternal caffeine consumption and adverse childhood metabolic outcomes. However, limited studies have examined neonate DNA methylation (DNAm) patterns in the context of preconception or prenatal exposure to caffeine metabolites.ObjectivesWe examined preconception and pregnancy caffeine exposure with DNAm alterations in neonate cord blood (n = 378).MethodsIn a secondary analysis of the Effects of Aspirin in Gestation and Reproduction Trial (EAGeR), we measured maternal caffeine, paraxanthine, and theobromine concentrations from stored serum collected preconception (on average 2 months before pregnancy) and at 8 weeks of gestation. In parallel, self-reported caffeinated beverage intake was captured via administration of questionnaires and daily diaries. We profiled DNAm from the cord blood buffy coat of singletons using the MethylationEPIC BeadChip. We assessed associations of maternal caffeine exposure and methylation β values using multivariable robust linear regression. A false discovery rate (FDR) correction was applied using the Benjamini-Hochberg method.ResultsIn preconception, the majority of women reported consuming 1 or fewer servings/day of caffeine on average, and caffeine and paraxanthine metabolite levels were 88 and 36 µmol/L, respectively. Preconception serum caffeine metabolites were not associated with individual cytosine-guanine (CpG) sites (FDR >5%), though pregnancy theobromine was associated with DNAm at cg09460369 near RAB2A (β = 0.028; SE = 0.005; FDR P = 0.012). Preconception self-reported caffeinated beverage intake compared to no intake was associated with DNAm at cg09002832 near GLIS3 (β = -0.013; SE = 0.002; FDR P = 0.036). No associations with self-reported intake during pregnancy were found.ConclusionsFew effects of maternal caffeine exposure on neonate methylation differences in leukocytes were identified in this population with relatively low caffeine consumption.

Project description:BackgroundAdverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates.ResultsData on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function.ConclusionsMaternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.

Dataset Information

Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs.

Publications

Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs.

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