Dna Methylation Mediates the Effect of Maternal Smoking During Pregnancy on Birthweight

Abstract

Background Research has shown that maternal smoking during pregnancy influences DNA methylation levels in the newborn, and epigenome-wide association studies have demonstrated several differentially methylated sites. Besides impacting methylation levels, maternal smoking during pregnancy results in a lower birthweight. Previous authors have proposed that these birthweight effects are mediated by DNA methylation. The aim of the present study was to test this hypothesis. Since methylation levels are partly sex-specific, separate analyses were performed in males and females. Methods Methylation levels in the cord blood of 325 newborns were determined using the Illumina HumanMethylation450 Beadchip. An epigenome-wide association study of maternal smoking was performed, based on m-values adjusted for covariates. To determine whether the association between birthweight and maternal smoking was attributable to methylation, mediation analyses were performed for the top hits controlling for smoking behavior, maternal diabetes, and gestational age. Sex-specific tests were also performed.Research has shown that maternal smoking during pregnancy influences DNA methylation levels in the newborn, and epigenome-wide association studies have demonstrated several differentially methylated sites. Besides impacting methylation levels, maternal smoking during pregnancy results in a lower birthweight. Previous authors have proposed that these birthweight effects are mediated by DNA methylation. The aim of the present study was to test this hypothesis. Since methylation levels are partly sex-specific, separate analyses were performed in males and females. Results After quality control, the sample comprised 309 newborns. Thirty mothers had smoked throughout the pregnancy. After correction for gestational age and sex, newborns whose mothers had smoked throughout pregnancy showed a > 200g lower birthweight than newborns with no history of maternal smoking. 44 differentially methylated CpGs with corrected p-values (FDR Discussion Our findings support an association between maternal smoking and differentially methylated CpG sites, and suggest that some of these methylation patterns partially mediate the influence of smoking on birthweight. Despite the influence of sex on some methylation level differences, no sex-dependent mediation effects were demonstrated.