Abstract
Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.
Highlights
Prenatal growth in humans has been linked to several complex disorders in adulthood
The current work suggests a putative link between both fetal growth and adult working memory (WM), and peripheral blood DNA methylation signatures at a region in the IGF2BP1 gene, in agreement with previous literature [51,52]
While the former reports separately detected associations between DNA methylation and either early development or WM, current results expand on the subject to indicate that, in the ongoing independent sample, relationships between IGF2BP1 DNA methylation and either birth weight (BW) or WM phenotypes are not confounded by each other
Summary
Prenatal growth in humans has been linked to several complex disorders in adulthood. In this regard, epidemiological studies demonstrate that poor intrauterine environment induces offspring phenotypes which are characterized by an increased risk of developing different chronic diseases [1]. Among the different epigenetic marks, DNA methylation is interesting in this context, since there is evidence that large inter-individual differences in methylation levels occur at regions covering mammalian developmental genes, and that this variability may correlate with phenotypic plasticity in changing environments [8]. Additional investigation on this topic has led to propose that some of these so-called variably methylated regions show temporal stability over periods of years and covary with individual traits [9], probably underlying the relationship between prenatal events and DNA methylation in adulthood [10]
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