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

Clin Epigenetics. 2018 Apr 17;10:55. doi: 10.1186/s13148-018-0488-x. eCollection 2018.

Abstract

Background: 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.

Methods: 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.

Results: 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 (C7orf50, ZAR1) 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 ACOT7 (4 sites), EPX (5 sites), EVL (3 sites), KSR1 (4 sites), ZFPM1 (3 sites), and ZNF862 (3 sites). Several of these methylation loci were previously associated with asthma (ADAM19, EPX, IL4, IL5RA, and PRG2).

Conclusion: 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.

Keywords: Epigenome-wide association studies; Life course analysis; Total serum IgE.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Child
  • Child, Preschool
  • Cohort Studies
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic
  • Epigenomics / methods*
  • Female
  • Fetal Blood / chemistry*
  • Genome-Wide Association Study / methods*
  • Humans
  • Hypersensitivity, Immediate / genetics*
  • Immunoglobulin E / genetics*
  • Longitudinal Studies
  • Male
  • Pregnancy
  • Prospective Studies

Substances

  • Immunoglobulin E