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Smoking Leaves a Historical Footprint in DNA

Summary: Researchers report DNA methylation could be an important sign that reveals a person’s smoking history, even years after they have quit.

Source: American Heart Association.

Smoking leaves its “footprint” on the human genome in the form of DNA methylation, a process by which cells control gene activity, according to new research in Circulation: Cardiovascular Genetics, an American Heart Association journal.

The new findings suggest that DNA methylation could be an important sign that reveals an individual’s smoking history, and could provide researchers with potential targets for new therapies

“These results are important because methylation, as one of the mechanisms of the regulation of gene expression, affects what genes are turned on, which has implications for the development of smoking-related diseases,” said Stephanie J. London, M.D., Dr.P.H., last author and deputy chief of the Epidemiology Branch at the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina. “Equally important is our finding that even after someone stops smoking, we still see the effects of smoking on their DNA.”

Smoking remains the leading preventable cause of death worldwide, despite a decline in smoking in many countries as a result of smoking cessation campaigns and legislative action. Even decades after stopping, former smokers are at long-term risk of developing diseases including some cancers, chronic obstructive pulmonary disease, and stroke. While the molecular mechanisms responsible for these long-term effects remain poorly understood, previous studies linking DNA methylation sites to genes involved with coronary heart disease and pulmonary disease suggest it may play an important role.

Researchers conducted a meta-analysis of DNA methylation sites across the human genome using blood samples taken from nearly 16,000 participants from 16 groups of the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium, including a group of the Framingham Heart Study that has been followed by researchers since 1971.

The researchers compared DNA methylation sites in current and former smokers to those who never smoked. They found:

  • Smoking-associated DNA methylation sites were associated with more than 7,000 genes, or one-third of known human genes.
  • For people who stopped smoking, the majority of DNA methylation sites returned to levels seen in never smokers within five years of quitting smoking.
  • However, some DNA methylation sites persisted even after 30 years of quitting.
  • The most statistically significant methylation sites were linked to genes enriched for association with numerous diseases caused by cigarette smoking, such as cardiovascular diseases and certain cancers.

The researchers suggest that some of these long-lasting methylation sites may be marking genes potentially important for former smokers who are still at increased risk of developing certain diseases. The discovery of smoking-related DNA methylation sites raises the possibility of developing biomarkers to evaluate a patient’s smoking history, as well as potentially developing new treatments targeted toward these methylation sites.

Image shows someone putting out a cigarette.

Smoking remains the leading preventable cause of death worldwide, despite a decline in smoking in many countries as a result of smoking cessation campaigns and legislative action. NeuroscienceNews.com image is credited to the American Heart Association.

The main analysis was not designed to examine effects over long periods of time. The researchers note, that this is the largest examination of the effects of smoking on DNA methylation.

“Our study has found compelling evidence that smoking has a long-lasting impact on our molecular machinery, an impact that can last more than 30 years,” said Roby Joehanes Ph.D. of Hebrew SeniorLife, first author and an instructor at Harvard Medical School in Boston, Massachusetts. “The encouraging news is that once you stop smoking, the majority of DNA methylation signals return to never smoker levels after five years, which means your body is trying to heal itself of the harmful impacts of tobacco smoking.”

About this neuroscience research article

Source: American Heart Association
Image Source: NeuroscienceNews.com image is credited to American Heart Association.
Original Research: Abstract for “Epigenetic Signatures of Cigarette Smoking” by 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 Shah, Allan F. McRae, Kurt Lohman, Jin 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, and Stephanie J. London in Circulation: Cardiovascular Genetics. Published online September 20 2016 doi:10.1161/CIRCGENETICS.116.001506

Cite This NeuroscienceNews.com Article
American Heart Association “Smoking Leaves a Historical Footprint in DNA.” NeuroscienceNews. NeuroscienceNews, 1 October 2016.
<http://neurosciencenews.com/smoking-genetics-dna-5175/>.
American Heart Association (2016, October 1). Smoking Leaves a Historical Footprint in DNA. NeuroscienceNew. Retrieved October 1, 2016 from http://neurosciencenews.com/smoking-genetics-dna-5175/
American Heart Association “Smoking Leaves a Historical Footprint in DNA.” http://neurosciencenews.com/smoking-genetics-dna-5175/ (accessed October 1, 2016).

Abstract

Epigenetic Signatures of Cigarette Smoking

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 2,433 current, 6,518 former, and 6,956 never smokers). Comparing current versus never smokers, 2,623 CpG sites (CpGs), annotated to 1,405 genes, were statistically significantly differentially methylated at Bonferroni threshold of p<1×10-7 (18,760 CpGs at False Discovery Rate (FDR)<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 (2,623 CpGs at FDR<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 biologic 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.

“Epigenetic Signatures of Cigarette Smoking” by 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 Shah, Allan F. McRae, Kurt Lohman, Jin 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, and Stephanie J. London in Circulation: Cardiovascular Genetics. Published online September 20 2016 doi:10.1161/CIRCGENETICS.116.001506

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