Epigenetic signatures of cigarette smoking

Joehanes, Roby, Just, Allan C., Marioni, Riccardo E., Pilling, Luke C., Reynolds, Lindsay M., Mandaviya, Pooja R., Guan, Weihua, Xu, Tao, Elks, Cathy E., Aslibekyan, Stella, Moreno-Macias, Hortensia, Smith, Jennifer A., Brody, Jennifer A., Dhingra, Radhika, Yousefi, Paul, Pankow, James S., Kunze, Sonja, Shah, Sonia H., McRae, Allan F., Lohman, Kurt, Sha, Jin, Absher, Devin M., Ferrucci, Luigi, Zhao, Wei, Demerath, Ellen W., Bressler, Jan, Grove, Megan L., Huan, Tianxiao, Liu, Chunyu, Mendelson, Michael M., Yao, Chen, Kiel, Douglas P., Peters, Annette, Wang-Sattler, Rui, Visscher, Peter M., Wray, Naomi R., Starr, John M., Ding, Jingzhong, Rodriguez, Carlos J., Wareham, Nicholas J., Irvin, Marguerite R., Zhi, Degui, Barrdahl, Myrto, Vineis, Paolo, Ambatipudi, Srikant, Uitterlinden, André G., Hofman, Albert, Schwartz, Joel, Colicino, Elena, Hou, Lifang, Vokonas, Pantel S., Hernandez, Dena G., Singleton, Andrew B., Bandinelli, Stefania, Turner, Stephen T., Ware, Erin B., Smith, Alicia K., Klengel, Torsten, Binder, Elisabeth B., Psaty, Bruce M., Taylor, Kent D., Gharib, Sina A., Swenson, Brenton R., Liang, Liming, Demeo, Dawn L., O'Connor, George T., Herceg, Zdenko, Ressler, Kerry J., Conneely, Karen N., Sotoodehnia, Nona, Kardia, Sharon L. R., Melzer, David, Baccarelli, Andrea A., Van Meurs, Joyce B. J., Romieu, Isabelle, Arnett, Donna K., Ong, Ken K., Liu, Yongmei, Waldenberger, Melanie, Deary, Ian J., Fornage, Myriam, Levy, Daniel and London, Stephanie J. (2016) Epigenetic signatures of cigarette smoking. Circulation: Cardiovascular Genetics, 9 5: 436-447. doi:10.1161/CIRCGENETICS.116.001506


Author Joehanes, Roby
Just, Allan C.
Marioni, Riccardo E.
Pilling, Luke C.
Reynolds, Lindsay M.
Mandaviya, Pooja R.
Guan, Weihua
Xu, Tao
Elks, Cathy E.
Aslibekyan, Stella
Moreno-Macias, Hortensia
Smith, Jennifer A.
Brody, Jennifer A.
Dhingra, Radhika
Yousefi, Paul
Pankow, James S.
Kunze, Sonja
Shah, Sonia H.
McRae, Allan F.
Lohman, Kurt
Sha, Jin
Absher, Devin M.
Ferrucci, Luigi
Zhao, Wei
Demerath, Ellen W.
Bressler, Jan
Grove, Megan L.
Huan, Tianxiao
Liu, Chunyu
Mendelson, Michael M.
Yao, Chen
Kiel, Douglas P.
Peters, Annette
Wang-Sattler, Rui
Visscher, Peter M.
Wray, Naomi R.
Starr, John M.
Ding, Jingzhong
Rodriguez, Carlos J.
Wareham, Nicholas J.
Irvin, Marguerite R.
Zhi, Degui
Barrdahl, Myrto
Vineis, Paolo
Ambatipudi, Srikant
Uitterlinden, André G.
Hofman, Albert
Schwartz, Joel
Colicino, Elena
Hou, Lifang
Vokonas, Pantel S.
Hernandez, Dena G.
Singleton, Andrew B.
Bandinelli, Stefania
Turner, Stephen T.
Ware, Erin B.
Smith, Alicia K.
Klengel, Torsten
Binder, Elisabeth B.
Psaty, Bruce M.
Taylor, Kent D.
Gharib, Sina A.
Swenson, Brenton R.
Liang, Liming
Demeo, Dawn L.
O'Connor, George T.
Herceg, Zdenko
Ressler, Kerry J.
Conneely, Karen N.
Sotoodehnia, Nona
Kardia, Sharon L. R.
Melzer, David
Baccarelli, Andrea A.
Van Meurs, Joyce B. J.
Romieu, Isabelle
Arnett, Donna K.
Ong, Ken K.
Liu, Yongmei
Waldenberger, Melanie
Deary, Ian J.
Fornage, Myriam
Levy, Daniel
London, Stephanie J.
Title Epigenetic signatures of cigarette smoking
Journal name Circulation: Cardiovascular Genetics   Check publisher's open access policy
ISSN 1942-3268
1942-325X
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1161/CIRCGENETICS.116.001506
Open Access Status Not yet assessed
Volume 9
Issue 5
Start page 436
End page 447
Total pages 12
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted 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.
Keyword Biomarkers
Genome-wide association study
Meta-analysis
Methylation
Smoking
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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