Birth weight associations with DNA methylation differences in an adult population

Rebecca A Madden,Daniel L Mccartney,Rosie M Walker,Robert F Hillary,Mairead L Bermingham,Konrad Rawlik,Stewart W Morris,Archie Campbell,David J Porteous,Ian J Deary,Kathryn L Evans,Jonathan Hafferty,Andrew M Mcintosh,Riccardo E Marioni

doi:10.1080/15592294.2020.1827713

Rebecca A Madden, Daniel L Mccartney + Show 12 more

Open Access

https://doi.org/10.1080/15592294.2020.1827713

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Abstract

ABSTRACT The Developmental Origins of Health and Disease (DOHaD) theory predicts that prenatal and early life events shape adult health outcomes. Birth weight is a useful indicator of the foetal experience and has been associated with multiple adult health outcomes. DNA methylation (DNAm) is one plausible mechanism behind the relationship of birth weight to adult health. Through data linkage between Generation Scotland and historic Scottish birth cohorts, and birth records held through the NHS Information and Statistics Division, a sample of 1,757 individuals with available birth weight and DNAm data was derived. Epigenome-wide association studies (EWAS) were performed in two independently generated DNAm subgroups (nSet1 = 1,395, nSet2 = 362), relating adult DNAm from whole blood to birth weight. Meta-analysis yielded one genome-wide significant CpG site (p = 5.97x10−9), cg00966482. There was minimal evidence for attenuation of the effect sizes for the lead loci upon adjustment for numerous potential confounder variables (body mass index, educational attainment, and socioeconomic status). Associations between birth weight and epigenetic measures of biological age were also assessed. Associations between lower birth weight and higher Grim Age acceleration (p(FDR) = 3.6x10−3) and shorter DNAm-derived telomere length (p(FDR) = 1.7x10−3) are described, although results for three other epigenetic clocks were null. Our results provide support for an association between birth weight and DNAm both locally at one CpG site, and globally via biological ageing estimates.

Highlights

The Developmental Origins of Health and Disease theory (DOHaD) states that through developmental plasticity, the foetal experience can permanently influ ence adult health [1]
We identified one epigenome-wide significant CpG site which is, to our knowledge, the first significant Epigenome-wide association studies (EWAS) result reported for birth weight in an adult sample
These results suggest differential methylation exists in adulthood related to birth weight, and this may be relevant to health and mortality

Summary

Introduction

The Developmental Origins of Health and Disease theory (DOHaD) states that through developmental plasticity, the foetal experience can permanently influ ence adult health [1]. The theory’s main proponent, David Barker, originally relied on birth weight as an Supplemental data for this article can be accessed here. Index of foetal nutrition – an assumption that has been contested by the awareness that multiple factors can influence birth weight [2]. Illness, and socioeconomic status [3,4,5] are among modifiable influences over offspring birth weight. Foetal genetics and maternal genetics both influence birthweight, the latter acting through the intrauterine environment [6,7]. Birth weight can be seen as an index of the general foetal experience

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