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Epigenetics Chromatin. 2016 Jun 29;9:25. doi: 10.1186/s13072-016-0074-4. eCollection 2016.

DNA methylation signature of human fetal alcohol spectrum disorder.

Author information

1
Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC Canada.
2
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC Canada.
3
Beaulieu-Saucier Pharmacogenomics Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC Canada.
4
Brain Research Centre, University of British Columbia, Vancouver, BC Canada.
5
Department of Pediatrics and Child Health, Faculty of Medicine, University of Manitoba, Winnipeg, MB Canada.
6
Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, MB Canada.
7
Faculty of Medicine, Université de Montréal, Montreal, QC Canada.
8
Centre for Neuroscience Studies, Queen's University, Kingston, ON Canada.
9
Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia Canada.
#
Contributed equally

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 remain 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.

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