Abstract Number: 172 | ID: 2017-172
Epigenome-Wide Meta-Analysis of DNA Methylation in Children related to Prenatal Particulate Air Pollution Exposure
Olena Gruzieva(The Institute of Environmental Medicine, Karolinska Institutet, Sweden, firstname.lastname@example.org), Carrie V. Breton(Department of Preventive Medicine, University of Southern California, United States), Herman T. den Dekker(The Generation R Study, Department of Paediatrics, Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, The Netherlands), Akram Ghantous(Epigenetics Group, International Agency for Research on Cancer, France), Allan C. Just(Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, United States), Michelle Plusquin(Centre of Environmental Sciences, Hasselt University, Belgium), José Luis Ruiz(Center for Genomic Regulation, Spain), Heather E. Volk(Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, United States), Andrea Baccarelli(Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, York, United States), Erik Melén(The Institute of Environmental Medicine, Karolinska Institutet, Sweden)Background/Aim: Exposure to air pollution has increasingly been associated with adverse effects on child health, particularly if experienced in utero or during infancy. Although the exact molecular responses to air pollution exposure during prenatal life are still not fully understood, epigenetic changes have been suggested as a link between early-life air pollution exposure and subsequent health end-points, including airway disease. In the present study we aimed to investigate associations between in utero exposure to particulate matter with an aerodynamic diameter of <10 µm (PM10) and <2.5 µm (PM2.5) and epigenome-wide DNA methylation in newborn children.
Methods: We meta-analyzed the associations of cord blood DNA methylation (Illumina 450K BeadChip) in nine European and North American studies with the mean estimated ambient exposure to PM10 (n=1949) and PM2.5 (n=1551) at maternal home addresses during pregnancy, with subsequent look-up analyses in children aged 8 years (n~1000). To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to both PM exposures in 16-year-olds from the Swedish birth cohort BAMSE (n=245).
Results: We found 6 CpG (cytosine-guanine dinucleotide) sites epigenome-wide significantly associated with prenatal PM10 exposure, and 14 CpG sites associated with prenatal PM2.5 exposure [false discovery rate (FDR) p<0.05] after adjustment for the estimated cord blood cell composition. Interestingly, two of the PM10-related sites mapped to genes FAM13A (cg00905156) and NOTCH4 (cg06849931) that have been previously associated with lung function and asthma phenotypes in genome-wide association studies (GWAS). These associations were also significant in the older children (p<0.05). PM10 exposure had a significant impact on NOTCH4 expression in adolescents (FDR p<0.05).
Conclusions: The differentially methylated CpG sites related to PM exposure found in our study may provide insights into mechanisms underlying adverse childhood health effect of air pollution, including complex diseases like asthma.