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

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
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.
2041-1723
Küpers, Leanne K.
733e94ec-9e37-450c-a8ca-e1adf2eec323
Monnereau, Claire
2cdfd719-8197-475e-adcb-2f00a13da387
Sharp, Gemma C.
1ca7cdb0-ff2c-4679-b625-d00e347fd140
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Rezwan, Faisal I
203f8f38-1f5d-485b-ab11-c546b4276338
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
et al.
Küpers, Leanne K.
733e94ec-9e37-450c-a8ca-e1adf2eec323
Monnereau, Claire
2cdfd719-8197-475e-adcb-2f00a13da387
Sharp, Gemma C.
1ca7cdb0-ff2c-4679-b625-d00e347fd140
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Rezwan, Faisal I
203f8f38-1f5d-485b-ab11-c546b4276338
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958

Monnereau, Claire and Sharp, Gemma C. , et al. (2019) Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight. Nature Communications, 10 (1), [1893]. (doi:10.1038/s41467-019-09671-3).

Record type: Article

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.

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More information

Accepted/In Press date: 18 February 2019
e-pub ahead of print date: 23 April 2019
Published date: 23 April 2019

Identifiers

Local EPrints ID: 430422
URI: http://eprints.soton.ac.uk/id/eprint/430422
ISSN: 2041-1723
PURE UUID: 2849f0b8-640c-425d-83dd-4e110c6e8370
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464
ORCID for Faisal I Rezwan: ORCID iD orcid.org/0000-0001-9921-222X

Catalogue record

Date deposited: 30 Apr 2019 16:30
Last modified: 26 Nov 2021 03:00

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Contributors

Author: Leanne K. Küpers
Author: Claire Monnereau
Author: Gemma C. Sharp
Author: John Holloway ORCID iD
Author: Faisal I Rezwan ORCID iD
Author: Syed Arshad
Corporate Author: et al.

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