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

Author:

Cobben Jan Maarten1,Krzyzewska Izabela M2,Venema Andrea2,Mul Adri N2,Polstra Abeltje2,Postma Alex V23,Smigiel Robert4,Pesz Karolina5,Niklinski Jacek6,Chomczyk Monika A6,Henneman Peter3,Mannens Marcel MAM3

Affiliation:

1. Department of Pediatrics, Amsterdam University Medical Centers, Location AMC, Emma Children's Hospital, Amsterdam, The Netherlands

2. Department of Clinical Genetics, Genome Diagnostics Laboratory, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands

3. Department of Anatomy, Embryology & Physiology, Amsterdam University Medical Centers, Location AMC, Amsterdam, The Netherlands

4. Department of Pediatrics & Rare Disorders, Medical University of Wroclaw, Poland

5. Department of Genetics, Medical University of Wroclaw, Poland

6. Department of Molecular Biology, Medical University of Bialystok, Poland

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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