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Brain weight in males is correlated with DNA methylation at IGF2

Molecular Psychiatry volume 15, pages 880–881 (2010)Cite this article

The insulin-like growth factor 2 (IGF2) gene, located in a cluster of imprinted genes on chromosome 11p15.5, encodes a hormone involved in prenatal growth and development. Impaired function of IGF2 is linked to intrauterine growth retardation,1 with aberrant imprinting of this region being associated with congenital disorders characterized by growth abnormalities such as Beckwith–Wiedermann Syndrome and Silver–Russell Syndrome.2 Epigenetic heterogeneity at IGF2 is also a known feature of normal populations,3 with variable imprinting reported in the brain4 and considerable loss of imprinting detected in fetal cerebellum samples.5 Several studies report that inter-individual differences in IGF2 methylation may be environmentally mediated, particularly by prenatal exposure to famine. Individuals conceived during the Dutch Hunger Winter Famine of 1944–1945 were found to be hypomethylated across a differentially methylated region (DMR) in IGF26 and at the insulin-IGF (INS_IGF) DNA transcript, which aligns with the 3′ end of the IGF2 gene.7 Of note, the authors report a significant interaction between DNA methylation and sex, with the association between IGF2 hypomethylation and famine exposure being restricted to males.7 It thus appears that variable IGF2 methylation may result from exposure to specific environmental factors during sensitive periods of development, and may be mediated by the sex of the exposed individual.

We hypothesized that variation in IGF2 methylation affecting gene dosage could impact upon the development of the brain, which continues to grow and mature after birth. The cerebellum, in particular, has a very long period of development; it begins differentiating at a very early stage, yet is one of the last brain structures to reach maturity,8 ultimately accounting for 10% of the total brain volume.9 In the present study, we assessed inter-individual differences in IGF2 methylation in the cerebellum using a set of post-mortem brain samples carefully characterized for brain weight, to determine whether a relationship exists between the degree of IGF2 methylation and total brain weight at death.

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  1. MRC SGDP Research Centre, Institute of Psychiatry, King's College London, London, UK

    R Pidsley, E L Dempster & J Mill

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  1. R Pidsley
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  2. E L Dempster
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Correspondence to J Mill.

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Pidsley, R., Dempster, E. & Mill, J. Brain weight in males is correlated with DNA methylation at IGF2. Mol Psychiatry 15, 880–881 (2010). https://doi.org/10.1038/mp.2009.138

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