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

Abstract

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\xa0with information regarding GMSDP and DNA methylation profiling at the birth of grandchildren (n\xa0=\xa0161) 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\xa0sites were differentially methylated in grandchildren\xa0because 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.