Abstract
Up to 13% of women may experience symptoms of depression during pregnancy or in the postpartum period. Depression during pregnancy has been associated with an increased risk of adverse neurodevelopmental outcomes in the child and epigenetic mechanisms could be one of the biological pathways to explain this association. In 844 mother–child pairs from the Avon Longitudinal Study of Parents and Children, we carried out an epigenome-wide association study (EWAS) to investigate associations between prospectively collected data on maternal depression ascertained by the Edinburgh Postnatal Depression Scale in pregnancy and DNA methylation in the cord blood of newborn offspring. In individual site analysis, we identified two CpG sites associated with maternal depression in the middle part of pregnancy. In our regional analysis, we identified 39 differentially methylated regions (DMRs). Seven DMRs were associated with depression at any time point during pregnancy, 7 associated with depression in mid-pregnancy, 23 were associated with depression in late pregnancy, and 2 DMRs were associated with depression throughout pregnancy. Several of these map to genes associated with psychiatric disease and brain development. We attempted replication in The Generation R Study and could not replicate our results. Although our findings in ALSPAC suggest that maternal depression could be associated with cord blood DNA methylation the results should be viewed as preliminary and hypothesis generating until further replicated in a larger sample.
Highlights
Up to 13% of women experience symptoms of depression during pregnancy or postpartum[1,2]
We looked up any maternal depression-associated CpG sites in a database of mQTLs41 previously identified in the cord blood of 771 ALSPAC children41. mQTLs were included in the database if the association between the SNP and the CpG had a p-value
Among the differentially methylated regions (DMRs) specific to depression throughout pregnancy we found 1 Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway but no enriched biological process Gene Ontology (GO) terms (FDR < 0.05)
Summary
Up to 13% of women experience symptoms of depression during pregnancy or postpartum[1,2]. Depression during pregnancy has been associated with an increased risk of adverse neurodevelopmental outcomes in the offspring[3,4,5]. The biological mechanisms behind the association between prenatal maternal depression and predisposition to later behavioural problems, learning difficulties, and psychiatric illness in the offspring have been extensively discussed, and it has been hypothesised, that epigenetic pathways could be one of the biological pathways involved[9]. Epigenetics is the study of potentially heritable molecular modifications to DNA and histone proteins that can affect gene expression without change to the underlying DNA sequence[10]. The most frequently studied epigenetic phenomenon is DNA methylation where CpG dinucleotides undergo a process of cytosine methylation which can alter chromatin accessibility and thereby gene transcription[10]
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