TY - JOUR
T1 - An epigenome-wide association meta-analysis of prenatal maternal stress in neonates
T2 - A model approach for replication
AU - Rijlaarsdam, Jolien
AU - Pappa, Irene
AU - Walton, Esther
AU - Bakermans-Kranenburg, Marian J.
AU - Mileva-Seitz, Viara R.
AU - Rippe, Ralph C.A.
AU - Roza, Sabine J.
AU - Jaddoe, Vincent W.V.
AU - Verhulst, Frank C.
AU - Felix, Janine F.
AU - Cecil, Charlotte A.M.
AU - Relton, Caroline L.
AU - Gaunt, Tom R.
AU - McArdle, Wendy
AU - Mill, Jonathan
AU - Barker, Edward D.
AU - Tiemeier, Henning
AU - van IJzendoorn, Marinus H.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Birth cohort
KW - cord blood
KW - DNA methylation
KW - epigenome-wide association study (EWAS)
KW - prenatal maternal stress
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U2 - 10.1080/15592294.2016.1145329
DO - 10.1080/15592294.2016.1145329
M3 - Article
C2 - 26889969
AN - SCOPUS:84961392813
VL - 11
SP - 140
EP - 149
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 2
ER -