Placental methylation signatures from maternal smoking during pregnancy and potential impacts on fetal growth: meta-analyses from 7 cohorts
Year: 2019
Type: conference-abstract
Abstract: PDS 71: Exposome, Johan Friso Foyer, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background/Aim: Maternal smoking during pregnancy (MSDP) causes adverse birth outcomes, is a major public health issue, and prior studies have observed a strong signature of prenatal tobacco exposure on the newborn methylome in cord blood. However, the placental methylome has not been as thoroughly studied, despite the placenta serving numerous critical functions related to fetal growth and development. We aimed to study the relationships between maternal smoking during pregnancy, placental DNA methylation, and birth outcomes within the Pregnancy and Childhood Epigenetics (PACE) Consortium. Methods: DNA methylation was measured at ~450,000 cytosine-phosphate-guanine (CpG) sites in placental tissues via the Illumina 450K array. We performed meta-analyses, first to estimate the associations between MSDP and placental DNA methylation (7 studies, N=1700, 344 exposed to any MSDP and 163 exposed to MSDP throughout the pregnancy), then to estimate the relationships between DNAm with birth weight and gestational age. We performed pathway enrichment analyses via ConsensusPathDB to gain insights into the placental processes that may be perturbed by tobacco smoke exposure. Results: We identified 1224 CpGs that were associated with MSDP (Bonferroni-adjusted), of which 298 were associated with gestational age and 43 associated birth weight (Bonferroni-adjusted); 141 were associated with gene expression in placental tissue (5%FDR). The most notable association was observed at cg27402634 which produced the strongest magnitude of association and smallest p-value (methylation difference = -22.95%, p-value = 5.35E-119, any versus no MSDP). Overall, the genes annotated to the MSDP-associated CpGs were enriched for processes and pathways that could plausibly be involved in the mechanisms of toxicity from prenatal tobacco smoke exposure, including growth-factor signaling, hormone activity, inflammatory cytokines and vascularization. Conclusions: We observed numerous relationships between the placental methylome, MSDP and birth outcomes. These may better inform the mechanisms through which MSDP impacts placental function and fetal growth.
Source: Environmental Epidemiology
Institutions: Emory University, Universitat Pompeu Fabra, Barcelona Institute of Science and Technology, Centre for Genomic Regulation, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Deakin University, The University of Melbourne, Murdoch Children's Research Institute, Harvard University, Massachusetts General Hospital, Dartmouth College, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, Université Grenoble Alpes, Barcelona Institute for Global Health
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,200
OpenAlex ID: W2982215180