Maternal Traits Link to Neonatal DNA Methylation of Metabolism and Immune Genes and Infant Adiposity

Background: Few studies have identified specific metabolic exposures in utero and established their connection with offspring adiposity via epigenetic mechanisms such as DNA methylation. We aimed to determine if maternal metabolic traits are associated with cord blood (CB) epigenetic signatures and, in turn, associate with infant adiposity. Methods: The Healthy Start study recruited 1,410 pregnant women from University of Colorado Hospital obstetric clinics from 2009-2014 using the following criteria: 16 years or older, singleton pregnancy less than 24 weeks, no history of extreme prematurity nor stillbirth, and no chronic medical conditions. Maternal serum samples at 28 weeks and cord blood samples were obtained from 588 dyads. DNA was extracted from stored buffy coats (-80 degrees Celsius) using the QIAamp DNA Blood Mini Kit (Qiagen). DNA purity, quality, and quantity were assessed using the Nanodrop 2000 spectrophotometer (ThermoFisher), the Bioanalyzer 2100 (Agilent) and the Qubit Fluorometer, (ThermoFisher). Samples of sufficient quality and quantity were bisulfite converted with the Zymo EZ DNA Methylation kit (Zymo Research). DNA methylation was evaluated with the Infinium 450K array. Using linear regression (R package) and Comb-p, CpGs in differentially methylated regions (DMRs) associating with maternal metabolic traits were interrogated for associations with offspring adiposity measured via air displacement plethysmography. Multiple correction testing was performed via Benjamini-Hochberg. Results: The largest number of significant CB DMRs were associated with maternal insulin (39, FDR