Birth weight, working memory and epigenetic signatures in IGF2 and related genes: a MZ twin study

PLoS One. 2014 Aug 29;9(8):e103639. doi: 10.1371/journal.pone.0103639. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Birth Weight*
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Insulin-Like Growth Factor II / genetics*
  • Memory, Short-Term / physiology*
  • Mosaicism
  • Pregnancy
  • Stochastic Processes
  • Twins, Monozygotic / genetics*

Substances

  • IGF2 protein, human
  • Insulin-Like Growth Factor II

Grants and funding

This work is supported by the Spanish SAF2008-05674-C03-01, European Twins Study Network on Schizophrenia Research Training Network (grant number EUTwinsS; MRTN-CT-2006-035987; local PIs: F.L. and N.I.), the Catalan 2014SGR1636 and the Ministry of Science and Innovation (PIM2010ERN-00642) in frame of ERA-NET NEURON. A.C.P. was funded by CONACyT (Mexico). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.