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

• Published in: International journal of molecular sciences 2020-10, Vol.21 (19), p.7201
• Main Authors: Gagné-Ouellet, Valérie, Breton, Edith, Thibeault, Kathrine, Fortin, Carol-Ann, Desgagné, Véronique, Girard Tremblay, Élise, Cardenas, Andres, Guérin, Renée, Perron, Patrice, Hivert, Marie-France, Bouchard, Luigi
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adiposity - genetics; Adult; Biomarkers; Body mass index; Child, Preschool; Childhood; Children; Chromosome 1; Chromosomes; Deoxyribonucleic acid; Deposition; Diabetes in children; DNA; DNA methylation; DNA Methylation - genetics; EPIC array; Epigenetic inheritance; Epigenetics; Epigenome - genetics; Female; fetal programming; Fetuses; Gene expression; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Gestational age; Glucose; Health aspects; Heterogeneity; Humans; Male; Metabolism; Mothers; mRNA; Obesity; Pediatric Obesity - genetics; Pediatric Obesity - pathology; Placenta; Placenta - metabolism; Placenta - pathology; Pregnancy; Regression analysis; Skinfold Thickness; skinfolds thickness; Thickness; transcriptomics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21197201

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.