RESEARCH on DNA/ EPIGENETICS in FASD

                                                                            RESEARCH ON FASD

 


 RESEARCH :  EFFECTIVENESS OF EVIDENCE-BASED TREATMENTS of FETAL ALCOHOL SPECTRUM DISORDERS (FASD) in children and adolescents:
                          A SYSTEMATIC REVIEW PROTOCOL

 

DNA SIGNATURE OF HUMAN FETAL ALCOHOL SPECTRUM DISORDER

ARTICLE

DNA methylation signature of human fetal alcohol spectrum disorder
Elodie Portales‑Casamar1†, Alexandre A. Lussier2†, Meaghan J. Jones2, Julia L. MacIsaac2, Rachel D. Edgar2,
Sarah M. Mah2, Amina Barhdadi3, Sylvie Provost3, Louis‑Philippe Lemieux‑Perreault3, Max S. Cynader4,
Albert E. Chudley5,6, Marie‑Pierre Dubé3,7, James N. Reynolds8, Paul Pavlidis1 and Michael S. Kobor2,9*
Abstract
Background:
Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which
may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol’s effects on
development remains relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the
range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects
of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort
of human FASD samples to date.
Methods: Genome-wide DNA methylation patterns of buccal epithelial cells (BECs) were analyzed using the Illumina
HumanMethylation450 array in a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed
in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip.
Results: After correcting for the effects of genetic background, we found 658 significantly differentially methylated
sites between FASD cases and controls, with 41 displaying differences in percent methylation change >5 %. Furthermore,
101 differentially methylated regions containing two or more CpGs were also identified, overlapping with 95
different genes. The majority of differentially methylated genes were highly expressed at the level of mRNA in brain
samples from the Allen Brain Atlas, and independent DNA methylation data from cortical brain samples showed high
correlations with BEC DNA methylation patterns. Finally, overrepresentation analysis of genes with up-methylated
CpGs revealed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy,
and autism spectrum disorders.
Conclusions: These findings suggested that prenatal alcohol exposure is associated with distinct DNA methylation
patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.