Association of grandmaternal smoking during pregnancy with DNA methylation of grandchildren: the Isle of Wight study

Background: To investigate the intergenerational effects of grandmaternal smoking during pregnancy (GMSDP) on the DNA methylation of grandchildren. Methods: Data from the Isle of Wight birth cohort with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n = 161) were used. Differentially methylated CpG sites related to GMSDP were identified using testing-training screening, analysis of variance and multivariate analysis of covariance. The association between identified CpG sites and expression levels of neighboring genes was tested by linear regression. Results: Twenty-three CpG sites were differentially methylated in grandchildren because of GMSDP, and eight of these were associated with expression levels of 13 neighboring genes. Conclusion: GMSDP has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy. Lay abstract This study aimed to assess how grandmaternal smoking during pregnancy can affect the health of grandchildren. Underlying mechanisms may include epigenetic modifications. To address this topic, the authors investigated the intergenerational effects of grandmaternal smoking during pregnancy on the DNA methylation of grandchildren at birth based on the Isle of Wight birth Cohort. Twenty-three CpG sites were differentially methylated in grandchildren because of grandmaternal smoking during pregnancy, and eight of these were associated with changes in expression levels of 13 neighboring genes. Thus, grandmaternal smoking during pregnancy has an intergenerational effect on the DNA methylation profile of grandchildren independent of maternal smoking during pregnancy.