Sex- and tissue-specific effects of binge levels of prenatal alcohol consumption on DNA methylation at birth

Lay abstract Women who binge-drink alcohol in pregnancy are more likely to have children with health and behavioural problems. It is possible that this happens through changes to the 'epigenetic' switches that control our genes. Yet few have tried to prove this. To test this idea, we designed a study called 'Asking QUestions about Alcohol in pregnancy'. We carefully measured levels of drinking across all trimesters in volunteers who were pregnant. Then we measured one type of 'gene switch' in cells from the placenta and from the cheeks of their babies. We did not find strong evidence that maternal binge drinking changed 'epigenetic' gene switches in babies. However, when we looked at female offspring only, we did find some evidence. The genes that we found had been seen by others in similar studies. Our findings have no immediate medical application but provide evidence for conducting larger studies. Background: Binge level prenatal alcohol exposure (PAE) causes developmental abnormalities, which may be mediated in part by epigenetic mechanisms. Despite this, few studies have characterised the association of binge PAE with DNA methylation in offspring. Methods: We investigated the association between binge PAE and genome-wide DNA methylation profiles in a sex-specific manner in neonatal buccal and placental samples. Results: We identified no differentially methylated CpGs or differentially methylated regions (DMRs) at false discovery rate <0.05. However, using a sum-of-ranks approach, we identified a DMR in each tissue of female offspring. The DMR identified in buccal samples is located near regions with previously-reported associations to fetal alcohol spectrum disorder (FASD) and binge PAE. Conclusion: Our findings warrant further replication and highlight a potential epigenetic link between binge PAE and FASD.