Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Nat Commun. 2016 Feb 10:7:10577. doi: 10.1038/ncomms10577.

Abstract

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina's HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cell Adhesion Molecules / genetics
  • Cytoskeletal Proteins / genetics
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Folic Acid / blood*
  • GPI-Linked Proteins / genetics
  • Gene Expression Regulation, Developmental*
  • Humans
  • Infant, Newborn
  • Kallikreins / genetics
  • LIM-Homeodomain Proteins / genetics
  • Monocarboxylic Acid Transporters / genetics
  • Peripherins / genetics
  • Pregnancy
  • Serine Endopeptidases / genetics
  • Transcription Factors / genetics

Substances

  • APC2 protein, human
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • GPI-Linked Proteins
  • LHX1 protein, human
  • LIM-Homeodomain Proteins
  • Monocarboxylic Acid Transporters
  • OPCML protein, human
  • PRPH protein, human
  • Peripherins
  • SLC16A12 protein, human
  • Transcription Factors
  • Folic Acid
  • Kallikreins
  • PRSS21 protein, human
  • Serine Endopeptidases
  • kallikrein 4