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Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Original publication

DOI

10.1038/s41467-019-09671-3

Type

Journal article

Journal

Nat Commun

Publication Date

23/04/2019

Volume

10

Keywords

Adolescent, Adult, Birth Weight, Body Mass Index, Child, CpG Islands, DNA, DNA Methylation, Epigenesis, Genetic, Female, Fetal Development, Fetus, Folic Acid, Genome, Human, Genome-Wide Association Study, Humans, Infant, Newborn, Male, Pregnancy, Prenatal Exposure Delayed Effects, Smoking