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Cumulative lifetime maternal stress and epigenome-wide placental DNA methylation in the PRISM cohort

Year: 2018
Type: article
Study design: Observational Study
Abstract: Evolving evidence links maternal stress exposure to changes in placental DNA methylation of specific genes regulating placental function that may have implications for the programming of a host of chronic disorders. Few studies have implemented an epigenome-wide approach. Using the Infinium HumanMethylation450 BeadChip (450K), we investigated epigenome-wide placental DNA methylation in relation to maternal experiences of traumatic and non-traumatic stressors over her lifetime assessed using the Life Stressor Checklist-Revised (LSC-R) survey (n = 207). We found differential DNA methylation at epigenome-wide statistical significance (FDR = 0.05) for 112 CpGs. Additionally, we observed three clusters that exhibited differential methylation in response to high maternal lifetime stress. Enrichment analyses, conducted at an FDR = 0.20, revealed lysine degradation to be the most significant pathway associated with maternal lifetimes stress exposure. Targeted enrichment analyses of the three largest clusters of probes, identified using the gap statistic, were enriched for genes associated with endocytosis (i.e., SMAP1, ANKFY1), tight junctions (i.e., EPB41L4B), and metabolic pathways (i.e., INPP5E, EEF1B2). These pathways, also identified in the top 10 KEGG pathways associated with maternal lifetime stress exposure, play important roles in multiple physiological functions necessary for proper fetal development. Further, two genes were identified to exhibit multiple probes associated with maternal lifetime stress (i.e., ANKFY1, TM6SF1). The methylation status of the probes belonging to each cluster and/or genes exhibiting multiple hits, may play a role in the pathogenesis of adverse health outcomes in children born to mothers with increased lifetime stress exposure.
Source: Epigenetics
DOI: 10.1080/15592294.2018.1497387
Authors: Kelly J. Brunst, Nicole Tignor, Allan Just, Zhonghua Liu, Xihong Lin, Michele R. Hacker, Michelle Bosquet Enlow, Robert O. Wright, Pei Wang, Andrea A. Baccarelli, Rosalind J. Wright
Institutions: University of Cincinnati, Icahn School of Medicine at Mount Sinai, Harvard University, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Columbia University
Language: English
Open Access status: bronze
Funders: Mount Sinai Health System, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: Perinatal Programming of Infant Stress Reactivity and the Atopic Phenotype, Prenatal stress and epigenetic programming of the HPA axis and autonomic balance, Prenatal Exposure to Endocrine Disrupters, DNA Methylation, and Childhood Obesity, Integrative multivariate association and genomic analyses, Mitochondrial Markers of Pollution, Stress, and Neurobehavior, MSHS Translational Science Hub, Proteo-genomic Discovery, Prioritization and Verification of Cancer Biomarkers, Statistical Methods for Integrative Analysis of Genomics and Proteomics Data, Stress-Air Pollution Interactions and Adolescent Neurobehavior, Mount Sinai Center for Health and Environment Across the LifeSpan (HEALS), Center for Environmental Health in Northern Manhattan
OpenAlex ID: W2883424607
FWCI: 2.096
Cites: 86
Cited by: 57
Related to: 10