DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13½ years: Project Ice Storm - PubMed (original) (raw)

DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13½ years: Project Ice Storm

Lei Cao-Lei et al. Epigenetics. 2015.

Abstract

Prenatal maternal stress (PNMS) in animals and humans predicts obesity and metabolic dysfunction in the offspring. Epigenetic modification of gene function is considered one possible mechanism by which PNMS results in poor outcomes in offspring. Our goal was to determine the role of maternal objective exposure and subjective distress on child BMI and central adiposity at 13½ years of age, and to test the hypothesis that DNA methylation mediates the effect of PNMS on growth. Mothers were pregnant during the January 1998 Quebec ice storm. We assessed their objective exposure and subjective distress in June 1998. At age 13½ their children were weighed and measured (n = 66); a subsample provided blood samples for epigenetic studies (n = 31). Objective and subjective PNMS correlated with central adiposity (waist-to-height ratio); only objective PNMS predicted body mass index (BMI). Bootstrapping analyses showed that the methylation level of genes from established Type-1 and -2 diabetes mellitus pathways showed significant mediation of the effect of objective PNMS on both central adiposity and BMI. However, the negative mediating effects indicate that, although greater objective PNMS predicts greater BMI and adiposity, this effect is dampened by the effects of objective PNMS on DNA methylation, suggesting a protective role of the selected genes from Type-1 and -2 diabetes mellitus pathways. We provide data supporting that DNA methylation is a potential mechanism involved in the long-term adaptation and programming of the genome in response to early adverse environmental factors.

Keywords: DNA methylation; Ice Storm; body mass index; central adiposity; mediating effect; prenatal maternal stress.

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Figures

Figure 1.

Figure 1.

Mediation analysis on the relationship between exposure to objective/subjective PNMS and growth outcomes. The path coefficients are known as the direct effects, indirect effects, and total effects. The direct effect indicates the effect of a risk factor on an outcome controlling for the mediators; the indirect effect (mediating effect) indicates the effect of the risk factor on an outcome variable through an intervening variable; the total effect is the full effect of risk factor on the outcome. It represents the sum of direct and indirect effects of the path. Path a is the effect of the objective/subjective PNMS (predictor variable) on the DNA methylation (mediator), path b is the effect of the DNA methylation on growth outcomes (outcome variable) controlling for the objective/subjective PNMS, and path c' is the direct effect of the objective/subjective PNMS on growth outcomes controlling for the DNA methylation. The path a*b indicates the indirect effect/mediating effect of objective/subjective PNMS on growth outcomes through DNA methylation (mediator). Path c is the total effect of objective/subjective PNMS on growth and obesity outcomes. This model can be represented by the following equation: c = c'+ a*b.

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