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 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.

Keywords::

• DNA methylation
• grandchildren
• grandmaternal smoking during pregnancy
• intergenerational effect
• smoking

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0433

R Luo tested hypotheses, conducted the analysis and drafted the manuscript. H Zhang contributed to the conception and interpretation of the data. N Mukherjee assisted with data analysis and interpretation of results. W Karmaus assisted with data interpretation and manuscript revision. V Patil was involved in manuscript revision. H Arshad was involved in sample collection, data acquisition, DNA methylation measurement in the Isle of Wight birth cohort and manuscript revision. F Mzayek designed the study, guided the analysis and was involved in the drafting and revision of the manuscript prior to submission. The manuscript has been read and approved by all authors.

Acknowledgments

The authors gratefully acknowledge the valuable effort of all staff at the David Hide Asthma and Allergy Research Centre in maintaining the Isle of Wight birth cohort. The authors also thank the team at the information technology services research computing office at the University of Memphis for their help in supporting high-performance computing. The authors would also like to thank the participants and their families, who have helped them over the last two decades.

Financial & competing interests disclosure

This study was funded by the NIH (grant number: R01 AI091905-01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate approval from the research ethics committee of the David Hide Asthma and Allergy Research Centre (reference number: 09/H0504/129) as well as the institutional review board at the University of Memphis (FWA00006815; 7 December 2012). In addition, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was funded by the NIH (grant number: R01 AI091905-01). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.