Richmond RC, et al. - Researchers determined if and how maternal smoke exposure impacts DNA methylation in long-term in 754 women (mean age 30 years). They also tried to reproduce findings in the same women 18 years later and in a cohort of 230 men (mean age 53 years). The extent to which a methylation score could predict prenatal smoke exposure was also investigated. They found robust evidence that demonstrated the persistence of the link between maternal smoking in pregnancy and changes in DNA methylation (in the exposed offspring) for many years after prenatal exposure.

Methods

• An epigenome-wide association analysis was carried out for prenatal smoke exposure.
• Researchers also conducted replication analyses for the top CpG sites in the other samples.
• Based on previously identified CpG sites, a DNA methylation score was derived.
• They assessed the performance of these scores as predictors of prenatal smoke exposure by producing receiver operating characteristic (ROC) curves.

Results

• The identified associations at 15 CpG sites in 11 gene regions were as follows: MYO1G, FRMD4A, CYP1A1, CNTNAP2, ARL4C, AHRR, TIFAB, MDM4, AX748264, DRD1, FTO (false discovery rate <5%).
• Researchers reported the following in regards to these links: most of these associations were specific to exposure during pregnancy, were present 18 years later and were replicated in a cohort of men.
• Prenatal smoke exposure could be predicted by a DNA methylation score (30 years previously) with an area under the curve of 0.72 (95% confidence interval 0.69, 0.76).