Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children.

Frey, Stefan; Eichler, Anna; Stonawski, Valeska; Kriebel, Jennifer; Wahl, Simone; Gallati, Sabina; Goecke, Tamme W; Fasching, Peter A; Beckmann, Matthias W; Kratz, Oliver; Moll, Gunther H; Heinrich, Hartmut; Kornhuber, Johannes; Golub, Yulia (2018). Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children. Frontiers in behavioral neuroscience, 12, p. 125. Frontiers Research Foundation 10.3389/fnbeh.2018.00125

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Prenatal alcohol exposure (PAE) is known to elicit a broad range of systemic effects, including neurophysiological alterations that result in adverse behavioral and cognitive outcomes. However, molecular pathways underlying these long-term intrauterine effects remain to be investigated. Here, we tested a hypothesis that PAE may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. We report the results of the study that included 156 primary school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. Thirty-two newborns were found to be exposed to alcohol with EtG values above 30 ng/g (EtG+). Previously we described PAE being associated with lower IQ and smaller amplitude of the event-related potential component P3 in go trials (Go-P3), which indicates a reduced capacity of attentional resources. Whole-genome methylation analysis of the buccal cell DNA revealed 193 differentially methylated genes in children with positive meconium EtG, that were clustered into groups involved in epigenetic modifications, neurodegeneration, neurodevelopment, axon guidance and neuronal excitability. Furthermore, we detected mediation effects of the methylation changes in and genes on the EtG related cognitive and attention-related deficits. Our results suggest that system-wide epigenetic changes are involved in long-term effects of PAE. In particular, we show an epigenetic mediation of PAE effects on cognition and attention-related processes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik

UniBE Contributor:

Gallati, Sabina

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1662-5153

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

André Schaller

Date Deposited:

12 Feb 2019 12:20

Last Modified:

26 Oct 2019 07:26

Publisher DOI:

10.3389/fnbeh.2018.00125

PubMed ID:

29997484

Uncontrolled Keywords:

ERP FRANCES IQ SLC16A9 attention dipeptidyl peptidase 10 (DPP10) prenatal alcohol exposure whole-genome DNA methylation

BORIS DOI:

10.7892/boris.123122

URI:

https://boris.unibe.ch/id/eprint/123122

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