DNA methylation as a predictor of fetal alcohol spectrum disorder
Abstract Background Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2–5%, F...
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doaj-5e04acde22cb4efd8b825b94cfa1e6d22020-11-25T02:47:32ZengBMCClinical Epigenetics1868-70751868-70832018-01-0110111410.1186/s13148-018-0439-6DNA methylation as a predictor of fetal alcohol spectrum disorderAlexandre A. Lussier0Alexander M. Morin1Julia L. MacIsaac2Jenny Salmon3Joanne Weinberg4James N. Reynolds5Paul Pavlidis6Albert E. Chudley7Michael S. Kobor8Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, British Columbia Children’s Hospital Research Institute, University of British ColumbiaDepartment of Medical Genetics, Centre for Molecular Medicine and Therapeutics, British Columbia Children’s Hospital Research Institute, University of British ColumbiaDepartment of Medical Genetics, Centre for Molecular Medicine and Therapeutics, British Columbia Children’s Hospital Research Institute, University of British ColumbiaDepartment of Pediatrics and Child Health, Faculty of Medicine, University of ManitobaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British ColumbiaDepartment of Biomedical and Molecular Sciences, Centre for Neuroscience Studies, Queen’s UniversityMichael Smith Laboratories, University of British ColumbiaDepartment of Pediatrics and Child Health, Faculty of Medicine, University of ManitobaDepartment of Medical Genetics, Centre for Molecular Medicine and Therapeutics, British Columbia Children’s Hospital Research Institute, University of British ColumbiaAbstract Background Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2–5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD. Building on our previous work identifying distinct DNA methylation patterns in children and adolescents with FASD, we have attempted to validate these associations in a different clinical cohort and to use our DNA methylation signature to develop a possible epigenetic predictor of FASD. Methods Genome-wide DNA methylation patterns were analyzed using the Illumina HumanMethylation450 array in the buccal epithelial cells of a cohort of 48 individuals aged 3.5–18 (24 FASD cases, 24 controls). The DNA methylation predictor of FASD was built using a stochastic gradient boosting model on our previously published dataset FASD cases and controls (GSE80261). The predictor was tested on the current dataset and an independent dataset of 48 autism spectrum disorder cases and 48 controls (GSE50759). Results We validated findings from our previous study that identified a DNA methylation signature of FASD, replicating the altered DNA methylation levels of 161/648 CpGs in this independent cohort, which may represent a robust signature of FASD in the epigenome. We also generated a predictive model of FASD using machine learning in a subset of our previously published cohort of 179 samples (83 FASD cases, 96 controls), which was tested in this novel cohort of 48 samples and resulted in a moderately accurate predictor of FASD status. Upon testing the algorithm in an independent cohort of individuals with autism spectrum disorder, we did not detect any bias towards autism, sex, age, or ethnicity. Conclusion These findings further support the association of FASD with distinct DNA methylation patterns, while providing a possible entry point towards the development of epigenetic biomarkers of FASD.http://link.springer.com/article/10.1186/s13148-018-0439-6Fetal alcohol spectrum disorderEpigeneticsDNA methylationBiomarkersNeurodevelopmental disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexandre A. Lussier Alexander M. Morin Julia L. MacIsaac Jenny Salmon Joanne Weinberg James N. Reynolds Paul Pavlidis Albert E. Chudley Michael S. Kobor |
spellingShingle |
Alexandre A. Lussier Alexander M. Morin Julia L. MacIsaac Jenny Salmon Joanne Weinberg James N. Reynolds Paul Pavlidis Albert E. Chudley Michael S. Kobor DNA methylation as a predictor of fetal alcohol spectrum disorder Clinical Epigenetics Fetal alcohol spectrum disorder Epigenetics DNA methylation Biomarkers Neurodevelopmental disorders |
author_facet |
Alexandre A. Lussier Alexander M. Morin Julia L. MacIsaac Jenny Salmon Joanne Weinberg James N. Reynolds Paul Pavlidis Albert E. Chudley Michael S. Kobor |
author_sort |
Alexandre A. Lussier |
title |
DNA methylation as a predictor of fetal alcohol spectrum disorder |
title_short |
DNA methylation as a predictor of fetal alcohol spectrum disorder |
title_full |
DNA methylation as a predictor of fetal alcohol spectrum disorder |
title_fullStr |
DNA methylation as a predictor of fetal alcohol spectrum disorder |
title_full_unstemmed |
DNA methylation as a predictor of fetal alcohol spectrum disorder |
title_sort |
dna methylation as a predictor of fetal alcohol spectrum disorder |
publisher |
BMC |
series |
Clinical Epigenetics |
issn |
1868-7075 1868-7083 |
publishDate |
2018-01-01 |
description |
Abstract Background Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2–5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD. Building on our previous work identifying distinct DNA methylation patterns in children and adolescents with FASD, we have attempted to validate these associations in a different clinical cohort and to use our DNA methylation signature to develop a possible epigenetic predictor of FASD. Methods Genome-wide DNA methylation patterns were analyzed using the Illumina HumanMethylation450 array in the buccal epithelial cells of a cohort of 48 individuals aged 3.5–18 (24 FASD cases, 24 controls). The DNA methylation predictor of FASD was built using a stochastic gradient boosting model on our previously published dataset FASD cases and controls (GSE80261). The predictor was tested on the current dataset and an independent dataset of 48 autism spectrum disorder cases and 48 controls (GSE50759). Results We validated findings from our previous study that identified a DNA methylation signature of FASD, replicating the altered DNA methylation levels of 161/648 CpGs in this independent cohort, which may represent a robust signature of FASD in the epigenome. We also generated a predictive model of FASD using machine learning in a subset of our previously published cohort of 179 samples (83 FASD cases, 96 controls), which was tested in this novel cohort of 48 samples and resulted in a moderately accurate predictor of FASD status. Upon testing the algorithm in an independent cohort of individuals with autism spectrum disorder, we did not detect any bias towards autism, sex, age, or ethnicity. Conclusion These findings further support the association of FASD with distinct DNA methylation patterns, while providing a possible entry point towards the development of epigenetic biomarkers of FASD. |
topic |
Fetal alcohol spectrum disorder Epigenetics DNA methylation Biomarkers Neurodevelopmental disorders |
url |
http://link.springer.com/article/10.1186/s13148-018-0439-6 |
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