Considering the impact of smoking on DNA methylation in Understanding Society
Smoking is a huge issue for social health and consequently there has been much research considering the relationship between tobacco use and many biological processes. One interesting field of study has identified epigenetic signatures of smoking using DNA methylation profiles. Up to this point, these studies were mostly carried out using the 450K BeadChip technology from Illumina. The new Infinium EPIC array is capable of quantifying DNA methylation at almost double the number of CpG sites and was used on whole blood from around 1200 participants of Understanding Society. This allowed integration of the household study’s rich smoking-related data with DNA methylation levels spanning the entire genome using linear modelling. The R package limma was used for this and allowed the identification of novel, smoking-associated loci in this study that were differentially methylated between smokers and non-smokers. These regressions also revealed a decrease in the number, and thus significance, of probes differentially methylated with smoking in former smokers compared to current smokers, supporting the idea than these changes are reversed upon cessation. Additionally, this study showed that DNA methylation levels within smokers varied with increasing dosage whereby duration of tobacco use appears to be more important than intensity in driving changes to the methylome caused by smoking. Furthermore, this differential methylation was reversed once a person had quit smoking and the degree of this decay increased with cessation years. Taking these findings, it was then possible to create two quantifiable DNA methylation-based biomarkers of smoking capable of predicting both years spent smoking in current smokers and years since quitting in former smokers. This may then prove to be a useful tool in characterising disease risk given the number of differentially methylated loci located in important health-related genes, especially if DNA methylation is indeed related to their expression.
Networked Digital Library of Theses and Dissertations