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Mediation by Placental DNA Methylation of the Association of Prenatal Maternal Smoking and Birth Weight.

Authors
  • Cardenas, Andres
  • Lutz, Sharon M
  • Everson, Todd M
  • Perron, Patrice
  • Bouchard, Luigi
  • Hivert, Marie-France
Type
Published Article
Journal
American journal of epidemiology
Publication Date
Nov 01, 2019
Volume
188
Issue
11
Pages
1878–1886
Identifiers
DOI: 10.1093/aje/kwz184
PMID: 31497855
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Prenatal maternal smoking is a risk factor for lower birth weight. We performed epigenome-wide association analyses of placental DNA methylation (DNAm) at 720,077 cytosine-phosphate-guanine (CpG) sites and prenatal maternal smoking among 441 mother-infant pairs (2010-2014) and evaluated whether DNAm mediates the association between smoking and birth weight using mediation analysis. Mean birth weight was 3,443 (standard deviation, 423) g, and 38 mothers (8.6%) reported smoking at a mean of 9.4 weeks of gestation. Prenatal maternal smoking was associated with a 175-g lower birth weight (95% confidence interval (CI): -305.5, -44.8) and with differential DNAm of 71 CpGs in placenta, robust to latent-factor adjustment reflecting cell types (Bonferroni-adjusted P < 6.94 × 10-8). Of the 71 CpG sites, 7 mediated the association between prenatal smoking and birth weight (on MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking × DNAm interactions on birth weight were observed for 5 CpG sites. The strongest mediator, cg22638236, was annotated to the PBX1 gene body involved in skeletal patterning and programming, with a mediated effect of 301-g lower birth weight (95% CI: -543, -86) among smokers but no mediated effect for nonsmokers (β = -38 g; 95% CI: -88, 9). Prenatal maternal smoking might interact with placental DNAm at specific loci, mediating the association with lower infant birth weight. © The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected]

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