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Epigenetics. 2016;11(2):140-9. doi: 10.1080/15592294.2016.1145329. Epub 2016 Feb 18.

An epigenome-wide association meta-analysis of prenatal maternal stress in neonates: A model approach for replication.

Author information

1
a Centre for Child and Family Studies, Leiden University , Leiden , the Netherlands.
2
b Generation R Study Group, Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands.
3
c Department of Child and Adolescent Psychiatry/ Psychology , Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands.
4
d School of Pedagogical and Educational Sciences, Erasmus University Rotterdam , Rotterdam , the Netherlands.
5
e Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , UK.
6
f Department of Psychiatry , Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands.
7
g Department of Epidemiology , Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands.
8
h Department of Pediatrics , Erasmus MC-University Medical Center Rotterdam , Rotterdam , the Netherlands.
9
i Medical Research Council Integrative Epidemiology Unit, University of Bristol , Bristol , UK.
10
j School of Social and Community Medicine, University of Bristol , Bristol , UK.
11
k University of Exeter Medical School, University of Exeter , Exeter , UK.

Abstract

Prenatal maternal stress exposure has been associated with neonatal differential DNA methylation. However, the available evidence in humans is largely based on candidate gene methylation studies, where only a few CpG sites were evaluated. The aim of this study was to examine the association between prenatal exposure to maternal stress and offspring genome-wide cord blood methylation using different methods. First, we conducted a meta-analysis and follow-up pathway analyses. Second, we used novel region discovery methods [i.e., differentially methylated regions (DMRs) analyses]. To this end, we used data from two independent population-based studies, the Generation R Study (n = 912) and the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 828), to (i) measure genome-wide DNA methylation in cord blood and (ii) extract a prenatal maternal stress composite. The meta-analysis (ntotal = 1,740) revealed no epigenome-wide (meta P <1.00e-07) associations of prenatal maternal stress exposure with neonatal differential DNA methylation. Follow-up analyses of the top hits derived from our epigenome-wide meta-analysis (meta P <1.00e-04) indicated an over-representation of the methyltransferase activity pathway. We identified no Bonferroni-corrected (P <1.00e-06) DMRs associated with prenatal maternal stress exposure. Combining data from two independent population-based samples in an epigenome-wide meta-analysis, the current study indicates that there are no large effects of prenatal maternal stress exposure on neonatal DNA methylation. Such replication efforts are essential in the search for robust associations, whether derived from candidate gene methylation or epigenome-wide studies.

KEYWORDS:

Birth cohort; DNA methylation; cord blood; epigenome-wide association study (EWAS); prenatal maternal stress

PMID:
26889969
PMCID:
PMC4846102
DOI:
10.1080/15592294.2016.1145329
[Indexed for MEDLINE]
Free PMC Article

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