Maternal Smoking during Pregnancy and DNA-Methylation in Children at Age 5.5 Years: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study

• Published in: PloS one 2016-05, Vol.11 (5), p.e0155554-e0155554
• Main Authors: Rzehak, Peter, Saffery, Richard, Reischl, Eva, Covic, Marcela, Wahl, Simone, Grote, Veit, Xhonneux, Annick, Langhendries, Jean-Paul, Ferre, Natalia, Closa-Monasterolo, Ricardo, Verduci, Elvira, Riva, Enrica, Socha, Piotr, Gruszfeld, Dariusz, Koletzko, Berthold
• Format: Article
• Language: English
• Subjects: Age; Bioinformatics; Biological effects; Biology and life sciences; Blood; Child; Childhood; Childhood obesity; Children; CpG islands; CpG Islands - genetics; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; DNA probes; Epidemiology; Epigenesis, Genetic; Epigenetics; Europe; Exposure; Female; Gene Regulatory Networks; Genes; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Gestation; Health aspects; Hospitals; Humans; Identification and classification; Infants; Intrauterine exposure; Male; Medicine; Medicine and Health Sciences; Metabolism; Methods; Nicotine; Obesity; Obesity - genetics; Phenotypes; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - genetics; Probes; Regression analysis; Risk factors; Signatures; Smoke; Smoking; Smoking - genetics; Smoking in pregnancy; Stability analysis; Studies; Tobacco; Tobacco smoke; Tobacco smoking
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0155554

Mounting evidence links prenatal exposure to maternal tobacco smoking with disruption of DNA methylation (DNAm) profile in the blood of infants. However, data on the postnatal stability of such DNAm signatures in childhood, as assessed by Epigenome Wide Association Studies (EWAS), are scarce. Objectives of this study were to investigate DNAm signatures associated with in utero tobacco smoke exposure beyond the 12th week of gestation in whole blood of children at age 5.5 years, to replicate previous findings in young European and American children and to assess their biological role by exploring databases and enrichment analysis. DNA methylation was measured in blood of 366 children of the multicentre European Childhood Obesity Project Study using the Illumina Infinium HM450 Beadchip (HM450K). An EWAS was conducted using linear regression of methylation values at each CpG site against in utero smoke exposure, adjusted for study characteristics, biological and technical effects. Methylation levels at five HM450K probes in MYO1G (cg12803068, cg22132788, cg19089201), CNTNAP2 (cg25949550), and FRMD4A (cg11813497) showed differential methylation that reached epigenome-wide significance according to the false-discovery-rate (FDR) criteria (q-value