title: Tobacco smoking leads to extensive genome-wide changes in DNA methylation.
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.
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Zeilinger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kühnel
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Baurecht
authors.forename: Anja
authors.initials: A
authors.lastname: Kleinschmidt
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Eva
authors.initials: E
authors.lastname: Lattka
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics; D000704:Analysis of Variance; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects*; D024202:Electrophoretic Mobility Shift Assay; D057890:Epigenomics / Q000379:methods; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D015894:Genome, Human / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018179:Receptors, Thrombin / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation / Q000706:statistics & numerical data; D013997:Time Factors
chemical_list: D000469:Alkaline Phosphatase; D051792:Basic Helix-Loop-Helix Proteins; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D018179:Receptors, Thrombin; D012097:Repressor Proteins; C492162:AHRR protein, human; C548269:ALPG protein, human; C019839:alkaline phosphatase, placental; C112908:protease-activated receptor 4