Epigenetic Signatures of Cigarette Smoking

By Roby Joehanes, A. Just, R. Marioni, L. Pilling, L. Reynolds, Pooja R Mandaviya, W. Guan, Tao Xu, C. Elks, S. Aslibekyan and 73 more. Circulation: Cardiovascular Genetics, 2016

798 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/23311b760548fd0f46a0143a1d7cabc0977562ae

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Citations in the corpus

An epigenetic biomarker of aging for lifespan and healthspan (2018, background): “Cigarette exposure has been shown to have an epigenetic fingerprint[35-37], which has been reflected in previous DNAm risk predictors[38].”
MethylNet: an automated and modular deep learning approach for DNA methylation analysis (2019, result): “…success of MethylNet to capture nonlinear interacting features that cluster, recapitulate and assist with predictions, we sought to evaluate MethylNet on the Liu data for the prediction of smoking status (current vs. never smoker) and compare the results to a prior robust EWAS meta-analysis [37].”
DNA methylation aging clocks: challenges and recommendations (2019, background): “Studies to date have assessed the combined contribution of genetic and epigenetic data to specific traits [123, 124] and have demonstrated the utility of using DNA methylation as an index of specific health-related exposures, notably smoking [125], to predict future disease risk [126].”