Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach.

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IgE-mediated sensitization may be epigenetically programmed in utero, but early childhood environment may further alter complex traits and disease phenotypes through epigenetic plasticity. However, the epigenomic footprint underpinning IgE-mediated type-I hypersensitivity has not been well-understood, especially under a longitudinal early-childhood life-course framework.


We used epigenome-wide DNA methylation (IlluminaHumanMethylation450 BeadChip) in cord blood and mid-childhood peripheral blood to investigate pre- and post-natal methylation marks associated with mid-childhood (age 6.7-10.2) total serum IgE levels in 217 mother-child pairs in Project Viva-a prospective longitudinal pre-birth cohort in eastern Massachusetts, USA. We identified methylation sites associated with IgE using covariate-adjusted robust linear regressions.


Nineteen methylation marks in cord blood were associated with IgE in mid-childhood (FDR < 0.05) in genes implicated in cell signaling, growth, and development. Among these, two methylation sites (, ) remained robust after the adjustment for the change in DNA methylation from birth to mid-childhood (FDR < 0.05). An analysis of the change in methylation between cord blood and mid-childhood DNA (Δ-DNAm) identified 395 methylation marks in 272 genes associated with mid-childhood IgE (FDR < 0.05), with multiple sites located within (4 sites), (5 sites), (3 sites), (4 sites), (3 sites), and (3 sites). Several of these methylation loci were previously associated with asthma (, , , , and ).


This study identified fetally programmed and mid-childhood methylation signals associated with mid-childhood IgE. Epigenetic priming during fetal development and early childhood likely plays an important role in IgE-mediated type-I hypersensitivity.

Clin Epigenetics
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Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach.
Peng C, Cardenas A, Rifas-Shiman SL, Hivert MF, Gold DR, Platts-Mills TA, Lin X, Oken E, Baccarelli AA, Litonjua AA, DeMeo DL