TPS 911: Air pollution, epigenetics, biomarkers, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM
Background: Cigarette smoke has genome-wide impacts on blood DNA methylation in newborns exposed to maternal smoking during pregnancy and in adults from their own smoking. However, it is not known whether there is a unique methylation signature for in utero exposure in newborns compared with personal smoking in adults.
Methods: We meta-analyzed blood DNA methylation, assessed with the Illumina450K array, in relation to sustained maternal smoking during pregnancy from 5,648 newborns (897 exposed) from the PACE (Pregnancy And Childhood Epigenetics) consortium. For adult blood DNA methylation and personal smoking, we meta-analyzed Illumina450K data from 15,907 participants (2,433 current smokers) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Cytosine-phosphate-Guanine (CpG) sites significantly (False Discovery Rate<5%) differentially methylated in relation to the relevant smoking exposure were compared to identify potentially unique methylation in newborns related to maternal smoking during pregnancy not seen for personal smoking in adults.
Results: There were 5,547 significantly differentially methylated CpG sites in relation to maternal smoking during pregnancy among the newborns. In adults, 34,541 CpG sites were significantly differentially methylated in relation to current smoking, reflecting the larger sample size and higher exposure proportion and thus higher power in the CHARGE data. We found 3,838 CpG sites that were significantly differentially methylated among the newborns only and 1,709 CpG sites overlapped between newborn and adult analyses. There were 743 genes with at least one significantly differentially methylated CpG site among the newborns but none among the adults. The unique smoking associated genes in newborns were enriched in pathways and processes related to metabolism of xenobiotics.
Conclusion: In addition to many shared signatures, we identified numerous signals specific to newborns. Our findings may provide new insights about the specific impacts on offspring of maternal smoking during pregnancy.