Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status

Abstract

This study evaluated the hypothesis that prenatal maternal socioeconomic status (SES) adversity is associated with DNA methylation in the placenta. SES adversity was defined by the presence of, as well as a summative count of, four factors: less than college education, single marital status, food and nutritional service assistance, and public health insurance. Epigenome-wide DNA methylation was assessed using the Illumina EPIC array in 426 placentas from a sample of infants born < 28 weeks of gestation from the Extremely Low Gestational Age Newborn cohort. Associations between SES adversity and DNA methylation were assessed with robust linear regressions adjusted for covariates and controlled the false discovery rate at < 10%. We also examined whether such associations were sex specific. Indicators of SES adversity were associated with differential methylation at 33 CpG sites. Of the 33 identified CpG sites, 19 (57.6%) displayed increased methylation, and 14 (42.4%) displayed decreased methylation in association with at least one of the SES adversity factors. Sex differences were observed in DNA methylation associated with summative SES score; in which placentas derived from female pregnancies showed more robust differential CpG methylation than placentas from male pregnancies. Maternal SES adversity was associated with differential methylation of genes with key role in gene transcription and placental function, potentially altering immunity and stress response. Further investigation is needed to evaluate the role of epigenetic differences in mediating the association between maternal socioeconomic status during pregnancy and later life health outcomes in children.

Epigenetics Underlying Susceptibility and Resilience Relating to Daily Life Stress, Work Stress, and Socioeconomic Status

“…Moreover, individuals who experienced a change in SES over their life span (based on the trajectory of father's occupational position as a proxy of early-life SES and individual highest occupational position as a proxy for adulthood SES) showed intermediate levels of accelerated epigenetic aging, indicating a potential reversibility of maladaptive epigenetic effects due to low SES. Notably, sex-dependent DNA methylation changes associated with SES have been demonstrated to already exist at the time of birth and to partially persist into early childhood (14,16), mainly affecting biological processes regulating immunological and developmental functions (10).…”

Evidence for the Placenta-Brain Axis: Multi-Omic Kernel Aggregation Predicts Intellectual and Social Impairment in Children Born Extremely Preterm

“…Samples were homogenized using a lysis buffer, and the homogenate was separated into aliquots. This process was detailed in a prior publication [27]. Nucleic acids were extracted from the homogenate using AllPrep DNA/RNA/miRNA Universal kit (Qiagen, Germany).…”

“…Extracted DNA sequences were bisulfate-converted using the EZ DNA methylation kit (Zymo Research, Irvine, CA) and followed by quantification using the Infinium MethylationEPIC BeadChip (Illumina, San Diego, CA), which measures CpG loci at a single nucleotide resolution, as previously described [26][27][28][29].…”

“…Quality control and normalization were performed resulting in 856,832 CpG probes from downstream analysis, with methylation represented as the average methylation level at a single CpG site ( -value) [27,[30][31][32]. DNA methylation data was imported into R for pre-processing using the minfi package [30].…”

“…Epigenome-wide associations (EWAS) of CpG methylation sites with outcomes were assessed using robust linear regression [45] with test statistic modification through an empirical Bayes procedure [42], described previously [27]. Both the differential mRNA and miRNA expression and EWAS models controlled for the following covariates: race, age, sex, number of gestational age days, birth weightscore, and education level of the mother.…”