Title: Associations between Maternal Tobacco Smoke Exposure and the Cord Blood [Formula: see text] DNA Methylome.
Authors: Howe, Caitlin G; Zhou, Meng; Wang, Xuting; Pittman, Gary S; Thompson, Isabel J; Campbell, Michelle R; Bastain, Theresa M; Grubbs, Brendan H; Salam, Muhammad T; Hoyo, Cathrine; Bell, Douglas A; Smith, Andrew D; Breton, Carrie V
Published In Environ Health Perspect, (2019 04)
Abstract: Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood.The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood [Formula: see text] DNA methylome.The methylomes of 20 Hispanic white newborns ([Formula: see text] exposed to any maternal tobacco smoke in pregnancy; [Formula: see text] unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: [Formula: see text]). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives).We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) [Formula: see text]]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented ([Formula: see text]) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult [Formula: see text] cells ([Formula: see text] smokers; [Formula: see text] nonsmokers), four replicated ([Formula: see text]). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: [Formula: see text] comparing exposed to unexposed) replicated ([Formula: see text]) in an EPIC (Illumina) array study of cord blood [Formula: see text] cells ([Formula: see text] exposed to sustained maternal tobacco smoke; [Formula: see text] unexposed) and in a study of adult [Formula: see text] cells across two platforms (EPIC: [Formula: see text] smokers; [Formula: see text] nonsmokers; 450K: [Formula: see text] smokers; [Formula: see text] nonsmokers).Maternal tobacco smoke exposure in pregnancy is associated with cord blood [Formula: see text] DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult [Formula: see text] cells. https://doi.org/10.1289/EHP3398.
PubMed ID: 31039056
MeSH Terms: Adult; CD4-Positive T-Lymphocytes/chemistry*; DNA Methylation/drug effects; Epigenome/drug effects*; Female; Fetal Blood/chemistry*; Humans; Male; Maternal Exposure*; Tobacco Smoke Pollution/analysis*; Young Adult