Abstract
BackgroundA low birth weight has been extensively related to poor adult health outcomes. Birth weight can be seen as a proxy for environmental conditions during prenatal development. Identical twin pairs discordant for birth weight provide an extraordinary model for investigating the association between birth weight and adult life health while controlling for not only genetics but also postnatal rearing environment. We performed an epigenome-wide profiling on blood samples from 150 pairs of adult monozygotic twins discordant for birth weight to look for molecular evidence of epigenetic signatures in association with birth weight discordance.ResultsOur association analysis revealed no CpG site with genome-wide statistical significance (FDR < 0.05) for either qualitative (larger or smaller) or quantitative discordance in birth weight. Even with selected samples of extremely birth weight discordant twin pairs, no significant site was found except for 3 CpGs that displayed age-dependent intra-pair differential methylation with FDRs 0.014 (cg26856578, p = 3.42e-08), 0.0256 (cg15122603, p = 1.25e-07) and 0.0258 (cg16636641, p = 2.05e-07). Among the three sites, intra-pair differential methylation increased with age for cg26856578 but decreased with age for cg15122603 and cg16636641. There was no genome-wide statistical significance for sex-dependent effects on intra-pair differential methylation in either the whole samples or the extremely discordant twins.ConclusionsGenome-wide DNA methylation profiling did not reveal epigenetic signatures of birth weight discordance although some sites displayed age-dependent intra-pair differential methylation in the extremely discordant twin pairs.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1062) contains supplementary material, which is available to authorized users.
Highlights
A low birth weight has been extensively related to poor adult health outcomes
According to the Barker hypothesis of Developmental Origins of Health and Disease (DOHaD), susceptibility to certain common diseases such as hypertension and type 2 diabetes may be related to poor environmental condition early in life [1,2]
In a recent epidemiological study on the birth weight discordant monozygotic twins included in the present study, Frost et al [5] found no effect of low birth weight on glucose metabolism
Summary
A low birth weight has been extensively related to poor adult health outcomes. Identical twin pairs discordant for birth weight provide an extraordinary model for investigating the association between birth weight and adult life health while controlling for genetics and postnatal rearing environment. According to the Barker hypothesis of Developmental Origins of Health and Disease (DOHaD), susceptibility to certain common diseases such as hypertension and type 2 diabetes may be related to poor environmental condition early in life [1,2]. In a recent epidemiological study on the birth weight discordant monozygotic twins included in the present study, Frost et al [5] found no effect of low birth weight on glucose metabolism. The inconsistent findings from epidemiological studies on disease endpoints call for new approaches in the search for evidences of an association between intrauterine growth and metabolic dysfunction
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