Abstract
Environmental factors such as tobacco smoking may have long-lasting effects on DNA methylation patterns, which might lead to changes in gene expression and in a broader context to the development or progression of various diseases. We conducted an epigenome-wide association study (EWAs) comparing current, former and never smokers from 1793 participants of the population-based KORA F4 panel, with replication in 479 participants from the KORA F3 panel, carried out by the 450K BeadChip with genomic DNA obtained from whole blood. We observed wide-spread differences in the degree of site-specific methylation (with p-values ranging from 9.31E-08 to 2.54E-182) as a function of tobacco smoking in each of the 22 autosomes, with the percent of variance explained by smoking ranging from 1.31 to 41.02. Depending on cessation time and pack-years, methylation levels in former smokers were found to be close to the ones seen in never smokers. In addition, methylation-specific protein binding patterns were observed for cg05575921 within AHRR, which had the highest level of detectable changes in DNA methylation associated with tobacco smoking (–24.40% methylation; p = 2.54E-182), suggesting a regulatory role for gene expression. The results of our study confirm the broad effect of tobacco smoking on the human organism, but also show that quitting tobacco smoking presumably allows regaining the DNA methylation state of never smokers.
Highlights
Epigenetic changes have been causally related to a variety of disease conditions including monogenic and complex multifactorial diseases [1]
A few studies have already been carried out with the Illumina 27K BeadChip [10,15], this array is limited by the fact that it only targets CpG sites located within the proximal promoter region of transcription start sites, with a focus on loci implicated in cancer
To investigate the effect of tobacco smoking on DNA methylation, we performed a genome-wide DNA methylation analysis with the Illumina 450K BeadChip using DNA obtained from whole blood
Summary
Epigenetic changes have been causally related to a variety of disease conditions including monogenic and complex multifactorial diseases [1]. The complex, dynamic and reactive mixture of an estimated 7,000 chemicals affects every organ system in the body and causes a wide spectrum of cardiovascular and chronic obstructive pulmonary diseases as well as various types of cancer, in particular lung cancer, through mechanisms that include DNA damage, inflammation, and oxidative stress [2,3,8,9]. It is insufficiently known how these mechanisms are triggered by tobacco smoking, but an association with altered DNA methylation patterns has been shown for a number of single genes, mostly cancer-related, and in genome-wide methylation studies [10–15]. Three studies concerning tobacco smoking have been accomplished with the 450K BeadChip, one using a small number of lymphoblasts and pulmonary macrophages of current and never smokers [12], another one using cord blood samples from newborns to study the effect of maternal smoking [16], and a very recent one that assessed the impact of current and former smoking on DNA methylation using whole blood samples from healthy individuals
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