Persistent epigenetic differences associated with prenatal exposure to famine in humans

Bastiaan T Heijmans; Elmar W Tobi; Aryeh D Stein; Hein Putter; Gerard J Blauw; Ezra S Susser; P Eline Slagboom; L H Lumey

doi:10.1073/pnas.0806560105

Lifestyle and Environment Nutrition and Metabolic Health

Persistent epigenetic differences associated with prenatal exposure to famine in humans

Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH

Published November 4, 2008 Proceedings of the National Academy of Sciences of the United States of America

DOI 10.1073/pnas.0806560105 PMID 18955703 PMC PMC2579375

RRM Academy Synopsis

Famine around conception was linked to lower IGF2 methylation

In a Dutch cohort of adults exposed to the 1944 to 1945 famine before birth, people exposed to famine around conception had lower IGF2 methylation 6 decades later. Each was compared with an unexposed same-sex sibling (60 pairs). Exposure late in pregnancy showed no difference in 62 pairs.

Key Findings

In 60 adults conceived during the famine, each compared with an unexposed same-sex sibling, average IGF2 methylation was 5.2% lower in the exposed person (0.48 standard deviations of the controls).
The exposed person had the lower IGF2 methylation in 72% (43/60) of sibships, and this appeared in conceptions across the famine period.
A repeat measurement of 46 of the 60 pairs, redoing the whole procedure, found a similar 5.6% lower methylation among the exposed.
In 62 people exposed late in pregnancy, average IGF2 methylation changed −0.9% against siblings (P = .64). The difference between timing groups was statistically significant (P interaction = 4.7 × 10⁻³).
People exposed late in pregnancy weighed 296 g less at birth than reference births (95% CI −420 to −170 g). People exposed around conception did not weigh less.

Interpretation

The Hunger Winter Families Study is an observational cohort. The study recruited people exposed to famine before birth, through live singleton births at three institutions in famine-exposed cities in 1945 and early 1946. Each exposed person was compared with a same-sex sibling for partial genetic matching. Researchers measured methylation at five sites in one region of the IGF2 gene, in adult blood samples, with group average ages from 57 to 59. The authors found no association between IGF2 methylation and birth weight (P = 0.39). They note that other stressors, such as cold and emotional stress, cannot be ruled out.

RRM Context

Restorative reproductive medicine counts the time around conception as part of reproductive health. The authors call early development a crucial period for setting epigenetic marks. They also name overnutrition as an exposure to study next.

Our editorial summary of this paper, not the article's abstract.

Abstract

Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.

Topics

Lifestyle and Environment

Nutrition and Metabolic Health Eating Disorders and Underfueling

Lifestyle and Environment › Nutrition and Metabolic Health › Eating Disorders and Underfueling

Bastiaan T Heijmans, Elmar W Tobi, Aryeh D Stein, Hein Putter, Gerard J Blauw, Ezra S Susser, P Eline Slagboom

B Heijmans, E Tobi, A Stein, H Putter, G Blauw, E Susser

PMID 18955703 18955703 DOI 10.1073/pnas.0806560105 10.1073/pnas.0806560105 Heijmans et al. 2008, Heijmans 2008

Persistent epigenetic differences associated with prenatal exposure to famine in humans

Famine around conception was linked to lower IGF2 methylation

Key Findings

Interpretation

RRM Context

Abstract

Topics

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