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

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 ( = -1.18, = 0.002 and = -0.82, = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at (r = -0.279, = 0.005) and (r = 0.216, = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction ( = -3.8 ± 4.1, = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within , , and 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.