DNA methylation mediates the effect of maternal smoking on offspring birthweight: a birth cohort study of multi-ethnic US mother-newborn pairs.

摘要: Maternal smoking affects more than half a million pregnancies each year in the US and is known to result fetal growth restriction as measured by lower birthweight its associated long-term consequences. also has been linked altered DNA methylation (DNAm). However, what remains largely unexplored whether these DNAm alterations are merely markers of exposure or if they have implications for health outcomes. This study tested hypothesis that mediates effect maternal on newborn birthweight. included mother–newborn pairs from predominantly urban, low-income multi-ethnic birth cohort. cord blood were determined using Illumina Infinium MethylationEPIC BeadChip. After standard quality control normalization procedures, an epigenome-wide association (EWAS) was performed linear regression models, controlling age, education, race, parity, pre-pregnancy body mass index, alcohol consumption, gestational pregestational/gestational diabetes, child sex, cell compositions batch effects. To quantify degree which smoking-birthweight association, VanderWeele-Vansteelandt approach single mediator structural equational model multiple mediators used, adjusting pertinent covariates. The 954 pairs. Among mothers, 165 (17.3%) ever smoked before during pregnancy. Newborns with had average 258 g newborns without (P < 0.001). Using false discovery rate (FDR) < 0.05 significance cutoff, EWAS identified 38 differentially methylated CpG sites smoking. Of those, 17 mapped previously reported genes: GFI1, AHRR, CYP1A1, CNTNAP2; 8 located first three genes, Bonferroni significantly mediated association. combined mediation genes explained 67.8% Our not only lends further support alters in a multiethnic population, but suggests substantially smoking–birthweight findings, validated, indicate modification likely important pathway impairs and, perhaps, even