Dataset Information

Epigenetic Signatures of Cigarette Smoking.

ABSTRACT: BACKGROUND:DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. METHODS AND RESULTS:To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15?907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10-7 (18?760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10-7 (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. CONCLUSIONS:Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

SUBMITTER: Joehanes R

PROVIDER: S-EPMC5267325 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Epigenetic Signatures of Cigarette Smoking.

Joehanes Roby R Just Allan C AC Marioni Riccardo E RE Pilling Luke C LC Reynolds Lindsay M LM Mandaviya Pooja R PR Guan Weihua W Xu Tao T Elks Cathy E CE Aslibekyan Stella S Moreno-Macias Hortensia H Smith Jennifer A JA Brody Jennifer A JA Dhingra Radhika R Yousefi Paul P Pankow James S JS Kunze Sonja S Shah Sonia H SH McRae Allan F AF Lohman Kurt K Sha Jin J Absher Devin M DM Ferrucci Luigi L Zhao Wei W Demerath Ellen W EW Bressler Jan J Grove Megan L ML Huan Tianxiao T Liu Chunyu C Mendelson Michael M MM Yao Chen C Kiel Douglas P DP Peters Annette A Wang-Sattler Rui R Visscher Peter M PM Wray Naomi R NR Starr John M JM Ding Jingzhong J Rodriguez Carlos J CJ Wareham Nicholas J NJ Irvin Marguerite R MR Zhi Degui D Barrdahl Myrto M Vineis Paolo P Ambatipudi Srikant S Uitterlinden André G AG Hofman Albert A Schwartz Joel J Colicino Elena E Hou Lifang L Vokonas Pantel S PS Hernandez Dena G DG Singleton Andrew B AB Bandinelli Stefania S Turner Stephen T ST Ware Erin B EB Smith Alicia K AK Klengel Torsten T Binder Elisabeth B EB Psaty Bruce M BM Taylor Kent D KD Gharib Sina A SA Swenson Brenton R BR Liang Liming L DeMeo Dawn L DL O'Connor George T GT Herceg Zdenko Z Ressler Kerry J KJ Conneely Karen N KN Sotoodehnia Nona N Kardia Sharon L R SL Melzer David D Baccarelli Andrea A AA van Meurs Joyce B J JB Romieu Isabelle I Arnett Donna K DK Ong Ken K KK Liu Yongmei Y Waldenberger Melanie M Deary Ian J IJ Fornage Myriam M Levy Daniel D London Stephanie J SJ

Circulation. Cardiovascular genetics 20160920 5

<h4>Background</h4>DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.<h4>Methods and results</h4>To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived D ...[more]

PMID: 27651444

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Project description:BackgroundMultiple studies have made robust associations between differential DNA methylation and exposure to cigarette smoke. But whether a DNA methylation phenotype is established immediately upon exposure, or only after prolonged exposure is less well-established. Here, we assess DNA methylation patterns from peripheral blood samples in current smokers in response to dose and duration of exposure, along with the effects of smoking cessation on DNA methylation in former smokers.MethodsDimensionality reduction was applied to DNA methylation data at 90 previously identified smoking-associated CpG sites for over 4900 individuals in the Generation Scotland cohort. K-means clustering was performed to identify clusters associated with current and never smoker status based on these methylation patterns. Cluster assignments were assessed with respect to duration of exposure in current smokers (years as a smoker), time since smoking cessation in former smokers (years), and dose (cigarettes per day).FindingsTwo clusters were specified, corresponding to never smokers (97·5% of whom were assigned to Cluster 1) and current smokers (81·1% of whom were assigned to Cluster 2). The exposure time point from which >50% of current smokers were assigned to the smoker-enriched cluster varied between 5 and 9 years in heavier smokers and between 15 and 19 years in lighter smokers. Low-dose former smokers were more likely to be assigned to the never smoker-enriched cluster in the first year following cessation. In contrast, a period of at least two years was required before the majority of former high-dose smokers were assigned to the never smoker-enriched cluster.InterpretationOur findings suggest that smoking-associated DNA methylation changes are a result of prolonged exposure to cigarette smoke, and can be reversed following cessation. The length of time in which these signatures are established and recovered is dose dependent. Should DNA methylation-based signatures of smoking status be predictive of smoking-related health outcomes, our findings may provide an additional criterion on which to stratify risk.

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Epigenetic Signatures of Cigarette Smoking.

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Epigenetic Signatures of Cigarette Smoking.

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