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

Publication ,  Journal Article
Martin, CL; Jima, D; Sharp, GC; McCullough, LE; Park, SS; Gowdy, KM; Skaar, D; Cowley, M; Maguire, RL; Fuemmeler, B; Collier, D; Relton, CL ...
Published in: Epigenetics
April 2019

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.

Duke Scholars

Published In

Epigenetics

DOI

EISSN

1559-2308

Publication Date

April 2019

Volume

14

Issue

4

Start / End Page

325 / 340

Location

United States

Related Subject Headings

  • Obesity
  • Metabolic Syndrome
  • Membrane Transport Proteins
  • Male
  • Infant, Newborn
  • Humans
  • Genome-Wide Association Study
  • Female
  • Epigenomics
  • Epigenesis, Genetic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Martin, C. L., Jima, D., Sharp, G. C., McCullough, L. E., Park, S. S., Gowdy, K. M., … Hoyo, C. (2019). Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study. Epigenetics, 14(4), 325–340. https://doi.org/10.1080/15592294.2019.1581594
Martin, Chantel L., Dereje Jima, Gemma C. Sharp, Lauren E. McCullough, Sarah S. Park, Kymberly M. Gowdy, David Skaar, et al. “Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study.Epigenetics 14, no. 4 (April 2019): 325–40. https://doi.org/10.1080/15592294.2019.1581594.
Martin, Chantel L., et al. “Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study.Epigenetics, vol. 14, no. 4, Apr. 2019, pp. 325–40. Pubmed, doi:10.1080/15592294.2019.1581594.
Martin CL, Jima D, Sharp GC, McCullough LE, Park SS, Gowdy KM, Skaar D, Cowley M, Maguire RL, Fuemmeler B, Collier D, Relton CL, Murphy SK, Hoyo C. Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study. Epigenetics. 2019 Apr;14(4):325–340.

Published In

Epigenetics

DOI

EISSN

1559-2308

Publication Date

April 2019

Volume

14

Issue

4

Start / End Page

325 / 340

Location

United States

Related Subject Headings

  • Obesity
  • Metabolic Syndrome
  • Membrane Transport Proteins
  • Male
  • Infant, Newborn
  • Humans
  • Genome-Wide Association Study
  • Female
  • Epigenomics
  • Epigenesis, Genetic