Epigenetic Signatures of Cigarette Smoking

Roby Joehanes, Allan C. Just, Riccardo E. Marioni, Luke C. Pilling, Lindsay M. Reynolds, Pooja R. Mandaviya, Weihua Guan, Tao Xu, Cathy E. Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A. Smith, Jennifer A. Brody, Radhika Dhingra, Paul Yousefi, James S. Pankow, Sonja Kunze, Sonia H. Shah, Allan F. McRae, Kurt LohmanJin Sha, Devin M. Absher, Luigi Ferrucci, Wei Zhao, Ellen W. Demerath, Jan Bressler, Megan L. Grove, Tianxiao Huan, Chunyu Liu, Michael M. Mendelson, Chen Yao, Douglas P. Kiel, Annette Peters, Rui Wang-Sattler, Peter M. Visscher, Naomi R. Wray, John M. Starr, Jingzhong Ding, Carlos J. Rodriguez, Nicholas J. Wareham, Marguerite R. Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G. Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S. Vokonas, Dena G. Hernandez, Andrew B. Singleton, Stefania Bandinelli, Stephen T. Turner, Erin B. Ware, Alicia K. Smith, Torsten Klengel, Elisabeth B. Binder, Bruce M. Psaty, Kent D. Taylor, Sina A. Gharib, Brenton R. Swenson, Liming Liang, Dawn L. Demeo, George T. O'Connor, Zdenko Herceg, Kerry J. Ressler, Karen N. Conneely, Nona Sotoodehnia, Sharon L.R. Kardia, David Melzer, Andrea A. Baccarelli, Joyce B.J. Van Meurs, Isabelle Romieu, Donna K. Arnett, Ken K. Ong, Yongmei Liu, Melanie Waldenberger, Ian J. Deary, Myriam Fornage, Daniel Levy, Stephanie J. London

Research output: Contribution to journalArticle

241 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)436-447
Number of pages12
JournalCirculation: Cardiovascular Genetics
Volume9
Issue number5
DOIs
StatePublished - Oct 1 2016

Keywords

  • biomarkers
  • genome-wide association study
  • meta-analysis
  • methylation
  • smoking

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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  • Cite this

    Joehanes, R., Just, A. C., Marioni, R. E., Pilling, L. C., Reynolds, L. M., Mandaviya, P. R., Guan, W., Xu, T., Elks, C. E., Aslibekyan, S., Moreno-Macias, H., Smith, J. A., Brody, J. A., Dhingra, R., Yousefi, P., Pankow, J. S., Kunze, S., Shah, S. H., McRae, A. F., ... London, S. J. (2016). Epigenetic Signatures of Cigarette Smoking. Circulation: Cardiovascular Genetics, 9(5), 436-447. https://doi.org/10.1161/CIRCGENETICS.116.001506