DNA methylation abundantly associates with fetal alcohol spectrum disorder and its subphenotypes

Epigenomics. 2019 May;11(7):767-785. doi: 10.2217/epi-2018-0221. Epub 2019 Mar 15.

Abstract

Aim: Fetal alcohol spectrum disorder (FASD) involves prenatal growth delay, impaired facial and CNS development and causes severe clinical, social-economic burdens. Here, we aim to detect DNA-methylation aberrations associated with FASD and potential FASD diagnostic and prognostic biomarkers. Patients & methods: The FASD diagnosis was established according to golden-standard protocols in a discovery and independent replication cohort. Genome-wide differential methylation association and replication analyses were performed. Results: We identified several loci that were robustly associated with FASD or one of its sub phenotypes. Our findings were evaluated using previously reported genome-wide surveys. Conclusion: We have detected robust FASD associated differentially methylated positions and differentially methylated regions for FASD in general and for FASD subphenotypes, in other words on growth delay, impaired facial and CNS development.

Keywords: 450K; DNA-methylation; epigenetic; fetal alcohol spectrum disorder; genome-wide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / metabolism
  • Case-Control Studies
  • Child
  • Child, Preschool
  • DNA Methylation*
  • Dystrophin-Associated Proteins / genetics
  • Female
  • Fetal Alcohol Spectrum Disorders / diagnosis*
  • Fetal Alcohol Spectrum Disorders / genetics
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Neuropeptides / genetics
  • Nuclear Proteins / genetics
  • Phenotype
  • Prognosis
  • Receptors, Tumor Necrosis Factor / genetics
  • Zinc Finger Protein Gli2 / genetics

Substances

  • Biomarkers
  • DTNA protein, human
  • Dystrophin-Associated Proteins
  • GLI2 protein, human
  • Neuropeptides
  • Nuclear Proteins
  • Receptors, Tumor Necrosis Factor
  • TNFRSF19 protein, human
  • Zinc Finger Protein Gli2