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The Dynamics of Smoking-Related Disturbed Methylation: A Two Time-Point Study of Methylation Change in Smokers, Non-Smokers and Former Smokers
Citation:
Wilson, R., S. Wahl, L. Pfeiffer, C. Ward-Caviness, S. Kunze, A. Kretschmer, E. Reischl, A. Peters, C. Gieger, AND M. Waldenberger. The Dynamics of Smoking-Related Disturbed Methylation: A Two Time-Point Study of Methylation Change in Smokers, Non-Smokers and Former Smokers. BMC Genomics. BioMed Central Ltd, London, Uk, 18(1):805, (2017).
Impact/Purpose:
This research article establishes the dynamics of the effect of smoking on genome-wide DNA methylation. It demonstrates that not only does smoking alter DNA methylation but that the rate of change from smoking and the rate of reversal after quitting smoking differs by DNA methylation locus. Some loci remain differentially methylated between non-smokers and former smokers many years after smoking cessation, and a select few continue to differentiate indicating potential lifetime effects of smoking on DNA methylation that may persist for decades. As smoking may mirror some environmental air pollution exposures in its effects this may help inform future studies of air pollution and health.
Description:
BACKGROUND: The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the lllumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker,·and those associated with continued smoking. RESULTS: Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. CONCLUSIONS: This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
