Placental DNA methylation and child lung function at 3-years

<bold>Background:</bold> The placenta is a key organ in fetal development and is involved in the link between maternal exposures and child health. Few studies have addressed the associations between placental DNA methylation and child respiratory health. <bold>Objective:</bold> To identify placental DNA methylation (DNAm) sites and regions associated with objective lung function parameters measured in 3-year-old children. <bold>Methods:</bold> The study is based on 280 mother-child couples participating in the French SEPAGES cohort. Placental DNAm levels were measured using the Infinium Methylation EPIC BeadChip. Standard and intra-breath airwave oscillometry (AOS) parameters (resistance at 7 Hz (R7), frequency-dependence of resistance (R7-19), reactance at 7 Hz (X7), area of the reactance curve (AX), and within-breath volume-dependence of resistance and reactance (ΔR, ΔX)) were measured. We used an adjusted robust linear regression model to identify differentially methylation sites and regions (DMR) associated with children AOS parameters. <bold>Results:</bold> Overall, 89 sites (false discovery rate <0.05) and 88 regions (p-value after Sidak correction < 0.05) were differentially methylated in relation to at least one AOS parameter, among which 35 sites and 70 DMR were robust to censoring of the extreme values (1% highest and lowest values of both DNAm and AOS). Nine DMR including 8 mapping to the <italic>CCDC163P</italic>, <italic>EIF2F</italic>, <italic>HSPD1</italic>, <italic>NPY</italic>, <italic>DLX6AS</italic>, <italic>SEC23IP</italic>, <italic>FKBP11</italic>, and <italic>EFS</italic> genes were associated with at least two AOS parameters. <bold>Conclusion:</bold> This study identified novel placental epigenetic loci associated with objective lung function parameters in young children. They may represent potential biomarkers of risk of suboptimal lung development. <italic>Funding: ANR-18-CE36-0005 ETAPE</italic>