Neonatal DNA methylation patterns associate with gestational age

James W. Schroeder, Karen N. Conneely, Joseph C. Cubells, Varun Kilaru, D. Jeffrey Newport, Bettina T. Knight, Zachary N. Stowe, Patricia A. Brennan, Julia Krushkal, Frances Tylavsky, Robert N. Taylor, Ronald M. Adkins, Alicia K. Smith

Research output: Contribution to journalArticle

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Abstract

Risk for adverse neonatal outcome increases with declining gestational age (GA), and changes in DNA methylation may contribute to the relationship between GA and adverse health outcomes in offspring. To test this hypothesis, we evaluated the association between GA and more than 27,000 CpG sites in neonatal DNA extracted from umbilical cord blood from two prospectively-characterized cohorts: (1) a discovery cohort consisting of 259 neonates from women with a history of neuropsychiatric disorders and (2) a replication cohort consisting of 194 neonates of uncomplicated mothers. GA was determined by obstetrician report and maternal last menstrual period. The associations between proportion of DNA methylated and GA were evaluated by fitting a separate linear mixed effects model for each CpG site, adjusting for relevant covariates including neonatal sex, race, parity, birth weight percentile and chip effects. CpG sites in 39 genes were associated with GA (false discovery rate <0.05) in the discovery cohort. The same CpG sites in 25 of these genes replicated in the replication cohort, with each association replicating in the same direction. Notably, these CpG sites were located in genes previously implicated in labor and delivery (e.g., AVP, OXT, CRHBP and ESR1) or that may influence the risk for adverse health outcomes later in life (e.g., DUOX2, TMEM176A and CASP8). All associations were independent of method of delivery or induction of labor. These results suggest neonatal DNA methylation varies with GA even in term deliveries. The potential contribution of these changes to clinically significant postnatal outcomes warrants further investigation.

Original languageEnglish (US)
Pages (from-to)1498-1504
Number of pages7
JournalEpigenetics
Volume6
Issue number12
DOIs
StatePublished - Jan 1 2011

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DNA Methylation
Gestational Age
Mothers
Newborn Infant
Induced Labor
Genes
DNA
Health
Parity
Fetal Blood
Birth Weight

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Schroeder, J. W., Conneely, K. N., Cubells, J. C., Kilaru, V., Jeffrey Newport, D., Knight, B. T., ... Smith, A. K. (2011). Neonatal DNA methylation patterns associate with gestational age. Epigenetics, 6(12), 1498-1504. https://doi.org/10.4161/epi.6.12.18296

Neonatal DNA methylation patterns associate with gestational age. / Schroeder, James W.; Conneely, Karen N.; Cubells, Joseph C.; Kilaru, Varun; Jeffrey Newport, D.; Knight, Bettina T.; Stowe, Zachary N.; Brennan, Patricia A.; Krushkal, Julia; Tylavsky, Frances; Taylor, Robert N.; Adkins, Ronald M.; Smith, Alicia K.

In: Epigenetics, Vol. 6, No. 12, 01.01.2011, p. 1498-1504.

Research output: Contribution to journalArticle

Schroeder, JW, Conneely, KN, Cubells, JC, Kilaru, V, Jeffrey Newport, D, Knight, BT, Stowe, ZN, Brennan, PA, Krushkal, J, Tylavsky, F, Taylor, RN, Adkins, RM & Smith, AK 2011, 'Neonatal DNA methylation patterns associate with gestational age', Epigenetics, vol. 6, no. 12, pp. 1498-1504. https://doi.org/10.4161/epi.6.12.18296
Schroeder JW, Conneely KN, Cubells JC, Kilaru V, Jeffrey Newport D, Knight BT et al. Neonatal DNA methylation patterns associate with gestational age. Epigenetics. 2011 Jan 1;6(12):1498-1504. https://doi.org/10.4161/epi.6.12.18296
Schroeder, James W. ; Conneely, Karen N. ; Cubells, Joseph C. ; Kilaru, Varun ; Jeffrey Newport, D. ; Knight, Bettina T. ; Stowe, Zachary N. ; Brennan, Patricia A. ; Krushkal, Julia ; Tylavsky, Frances ; Taylor, Robert N. ; Adkins, Ronald M. ; Smith, Alicia K. / Neonatal DNA methylation patterns associate with gestational age. In: Epigenetics. 2011 ; Vol. 6, No. 12. pp. 1498-1504.
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