Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age

Abstract

The aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear regression models adjusted for gestational age, child’s sex, age at follow-up and cellular heterogeneity. We sought replication of DNAm association with child adiposity in an independent cohort. We quantified placental mRNA levels for annotated gene using qRT-PCR and tested for correlation with DNAm. Lower DNAm at cg22593959 and cg22436429 was associated with higher adiposity (β = −1.18, q = 0.002 and β = −0.82, q = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the TFAP2E gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at FAM3C (rs = −0.279, p = 0.005) and TFAP2E (rs = 0.216, p = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction (β = −3.8 ± 4.1, p = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within FMN1, MAGI2, SKAP2 and BMPR1B genes. We identified placental epigenetic variations associated with adiposity at 3 years of age suggesting that childhood fat accretion patterns might be established during fetal life.

Detecting cord blood cell type-specific epigenetic associations with gestational diabetes mellitus and early childhood growth

“…For the current study, we analyzed 275 mother–child pairs of European ancestry with delivery that occurred ≥ 37 weeks of gestation, and had measured weight and height of children upon a return visit at the age of 3 when the offspring were aged 40.5 ± 3.0 months [ 25 ]. Weight was measured with a calibrated electronic scale with bare feet in light clothing.…”

Identification of key genes related to intramuscular fat deposition in Beijing-You chicken by mRNA and miRNA transcriptome analysis

“…In addition, there was a significantly negative correlation between BMPR1B and PL (r = -0.74, P < 0.05). Recent studies have shown that BMPR1B is associated with fat deposition in children ( Gagné et al, 2020 ). To date, no studies have directly shown that miR-6701-3p, miR-449c/d-5p, and miR-1563 are associated with adipogenesis.…”

Recent progress in epigenetics of obesity

“…These results suggest that maternal obesity is associated with the down-regulation and epigenetic alterations of leptin/adiponectin in the placenta, providing new ideas for great understanding of the mechanisms of obesity. Gagné-Ouellet et al [ 65 ] identified placental DNAm variation associated with adiposity at 3 years of age. Placental DNAm and mRNA levels for the annotated gene were quantified in 262 mother–offspring.…”

“…SAM is converted to S-adenosylhomocysteine (SAH) control, metabolism, insulin signaling, and obesity or related phenotypes [8,9]. Currently, the most commonly used biological samples for DNAm detection are blood samples including whole blood and leukocytes , adipose tissues [16,[54][55][56][57][58][59], skeletal muscles [60][61][62][63], placenta [64][65][66][67][68] and saliva [69][70][71][72][73] etc. (Fig.…”