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Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-019-09671-3

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Role:
Author
ORCID:
0000-0001-9850-5215
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Role:
Author
ORCID:
0000-0003-2906-4035
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Role:
Author
ORCID:
0000-0002-2279-4097


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
10
Article number:
1893
Publication date:
2019-04-23
Acceptance date:
2019-02-18
DOI:
EISSN:
2041-1723
Pmid:
31015461


Language:
English
Keywords:
Pubs id:
pubs:995727
UUID:
uuid:58a571a4-59c7-42f2-9365-5a71fa55d259
Local pid:
pubs:995727
Source identifiers:
995727
Deposit date:
2019-06-11
ARK identifier:

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