The dynamics of smoking-related disturbed methylation: a two time-point study of methylation change in smokers, non-smokers and former smokers

Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of t...

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Published in:BMC genomics Vol. 18; no. 1; pp. 805 - 15
Main Authors: Wilson, Rory, Wahl, Simone, Pfeiffer, Liliane, Ward-Caviness, Cavin K., Kunze, Sonja, Kretschmer, Anja, Reischl, Eva, Peters, Annette, Gieger, Christian, Waldenberger, Melanie
Format: Journal Article
Language:English
Published: London BioMed Central 18.10.2017
BioMed Central Ltd
Springer Nature B.V
BMC
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ISSN:1471-2164, 1471-2164
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Abstract Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Results Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p -value 3.61 x 10 -39 for cg26703534, gene AHRR ). Most of these sites’ respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. Conclusions This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
AbstractList Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Results Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites’ respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. Conclusions This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Results Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p -value 3.61 x 10 -39 for cg26703534, gene AHRR ). Most of these sites’ respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. Conclusions This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
Abstract Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Results Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites’ respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. Conclusions This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking.BACKGROUNDThe evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking.Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive.RESULTSOur results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive.This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.CONCLUSIONSThis study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10.sup.-39 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease.
Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale investigations have explored the associations using observations for individuals at multiple time-points. Here, through the use of the Illumina 450K BeadChip and data collected at two time-points separated by approximately 7 years, we investigate changes in methylation over time associated with quitting smoking or remaining a former smoker, and those associated with continued smoking. Results Our results indicate that after quitting smoking the most rapid reversion of altered methylation occurs within the first two decades, with reversion rates related to the initial differences in methylation. For 52 CpG sites, the change in methylation from baseline to follow-up is significantly different for former smokers relative to the change for never smokers (lowest p-value 3.61 x 10.sup.-39 for cg26703534, gene AHRR). Most of these sites' respective regions have been previously implicated in smoking-associated diseases. Despite the early rapid change, dynamism of methylation appears greater in former smokers vs never smokers even four decades after cessation. Furthermore, our study reveals the heterogeneous effect of continued smoking: the methylation levels of some loci further diverge between smokers and non-smokers, while others re-approach. Though intensity of smoking habit appears more significant than duration, results remain inconclusive. Conclusions This study improves the understanding of the dynamic link between cigarette smoking and methylation, revealing the continued fluctuation of methylation levels decades after smoking cessation and demonstrating that continuing smoking can have an array of effects. The results can facilitate insights into the molecular mechanisms behind smoking-induced disturbed methylation, improving the possibility for development of biomarkers of past smoking behavior and increasing the understanding of the molecular path from exposure to disease. Keywords: DNA methylation, Smoking, Longitudinal study, Epigenetics, Tobacco, Cigarettes
ArticleNumber 805
Audience Academic
Author Kunze, Sonja
Reischl, Eva
Wahl, Simone
Wilson, Rory
Waldenberger, Melanie
Ward-Caviness, Cavin K.
Pfeiffer, Liliane
Peters, Annette
Kretschmer, Anja
Gieger, Christian
Author_xml – sequence: 1
  givenname: Rory
  orcidid: 0000-0001-6135-3764
  surname: Wilson
  fullname: Wilson, Rory
  email: rory.wilson@helmholtz-muenchen.de
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Research Unit Molecular Epidemiology (AME)
– sequence: 2
  givenname: Simone
  surname: Wahl
  fullname: Wahl, Simone
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, German Center for Diabetes Research (DZD e.V.)
– sequence: 3
  givenname: Liliane
  surname: Pfeiffer
  fullname: Pfeiffer, Liliane
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
– sequence: 4
  givenname: Cavin K.
  surname: Ward-Caviness
  fullname: Ward-Caviness, Cavin K.
  organization: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Environmental Public Health Division, US Environmental Protection Agency
– sequence: 5
  givenname: Sonja
  surname: Kunze
  fullname: Kunze, Sonja
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
– sequence: 6
  givenname: Anja
  surname: Kretschmer
  fullname: Kretschmer, Anja
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
– sequence: 7
  givenname: Eva
  surname: Reischl
  fullname: Reischl, Eva
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
– sequence: 8
  givenname: Annette
  surname: Peters
  fullname: Peters, Annette
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance
– sequence: 9
  givenname: Christian
  surname: Gieger
  fullname: Gieger, Christian
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, German Center for Diabetes Research (DZD e.V.)
– sequence: 10
  givenname: Melanie
  surname: Waldenberger
  fullname: Waldenberger, Melanie
  organization: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29047347$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords DNA methylation
Epigenetics
Tobacco
Cigarettes
Longitudinal study
Smoking
Language English
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Snippet Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few...
The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few large-scale...
Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies. However, few...
Abstract Background The evidence for epigenome-wide associations between smoking and DNA methylation continues to grow through cross-sectional studies....
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SubjectTerms Age
Animal Genetics and Genomics
Biomarkers
Biomedical and Life Sciences
Blood
Cigarette smoking
Cigarettes
CpG islands
Deoxyribonucleic acid
DNA
DNA Methylation
Drug addiction
Epigenetics
Female
Genetic aspects
Genomics
Habits
Health aspects
Human and rodent genomics
Humans
Interviews
Life Sciences
Longitudinal studies
Longitudinal study
Male
Methylation
Microarrays
Microbial Genetics and Genomics
Middle Aged
Molecular modelling
Oligonucleotide Array Sequence Analysis
Plant Genetics and Genomics
Principal components analysis
Proteomics
Research Article
Reversion
Smokers
Smoking
Smoking - genetics
Smoking cessation
Time Factors
Tobacco
Variation
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Title The dynamics of smoking-related disturbed methylation: a two time-point study of methylation change in smokers, non-smokers and former smokers
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