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Epigenetics. 2019 Feb 18. doi: 10.1080/15592294.2019.1581594. [Epub ahead of print]

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study.

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a Department of Epidemiology , Gillings School of Global Public Health, 135 Dauer Drive Campus Box #7400, University of North Carolina , Chapel Hill , NC , 27599 , USA.
b Center of Human Health and the Environment, North Carolina State University , Raleigh , 27695 , USA.
c Bioinformatics Research Center, North Carolina State University , Raleigh , NC 27695 , USA.
d Medical Research Integrative Epidemiology Unit, Bristol Medical School, Population Health Sciences, University of Bristol , Bristol , BS8 2BN , UK.
e Department of Epidemiology , Rollins School of Public Health, Emory University , Atlanta , GA , 30322 , USA.
f Department of Biological Sciences , North Carolina State University , Raleigh , NC , 27695 , USA.
g Department of Pharmacology and Toxicology , Brody School of Medicine, East Carolina University , Greenville , NC , 27834 , USA.
h Department of Health Behavior and Policy , Virginia Commonwealth University , Richmond , VA , 23219 , USA.
i Department of Pediatrics , Brody School of Medicine, East Carolina University , Greenville , NC , 27858 , USA.
j Division of Reproductive Sciences, Department of Obstetrics and Gynecology , Duke University School of Medicine , Durham , NC , 27708 , USA.


Pre-pregnancy obesity is an established risk factor for adverse sex-specific cardiometabolic health in offspring. Epigenetic alterations, such as in DNA methylation (DNAm), are a hypothesized link; however, sex-specific epigenomic targets remain unclear. Leveraging data from the Newborn Epigenetics Study (NEST) cohort, linear regression models were used to identify CpG sites in cord blood leukocytes associated with pre-pregnancy obesity in 187 mother-female and 173 mother-male offsprings. DNAm in cord blood was measured using the Illumina HumanMethylation450k BeadChip. Replication analysis was conducted among the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Associations between pre-pregnancy obesity-associated CpG sites and offspring BMI z-score (BMIz) and blood pressure (BP) percentiles at 4-5-years of age were also examined. Maternal pre-pregnacy obesity was associated with 876 CpGs in female and 293 CpGs in male offspring (false discovery rate <5%). Among female offspring, 57 CpG sites, including the top 18, mapped to the TAPBP gene (range of effect estimates: -0.83% decrease to 4.02% increase in methylation). CpG methylation differences in the TAPBP gene were also observed among males (range of effect estimates: -0.30% decrease to 2.59% increase in methylation). While technically validated, none of the TAPBP CpG sites were replicated in ALSPAC. In NEST, methylation differences at CpG sites of the TAPBP gene were associated with BMI z-score (cg23922433 and cg17621507) and systolic BP percentile (cg06230948) in female and systolic (cg06230948) and diastolic (cg03780271) BP percentile in male offspring. Together, these findings suggest sex-specific effects, which, if causal, may explain observed sex-specific effects of maternal obesity.


ALSPAC; DNA methylation; NEST; cardiometabolic health; epigenome-wide association study; maternal obesity; offspring blood pressure; offspring body mass index

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