Dataset Information

The Effect of Tobacco Smoking Differs across Indices of DNA Methylation-Based Aging in an African American Sample: DNA Methylation-Based Indices of Smoking Capture These Effects.

ABSTRACT: Smoking is one of the leading preventable causes of morbidity and mortality worldwide, prompting interest in its association with DNA methylation-based measures of biological aging. Considerable progress has been made in developing DNA methylation-based measures that correspond to self-reported smoking status. In addition, assessment of DNA methylation-based aging has been expanded to better capture individual differences in risk for morbidity and mortality. Untested to date, however, is whether smoking is similarly related to older and newer indices of DNA methylation-based aging, and whether DNA methylation-based indices of smoking can be used in lieu of self-reported smoking to examine effects on DNA methylation-based aging measures. In the current investigation we examine mediation of the impact of self-reported cigarette consumption on accelerated, intrinsic DNA methylation-based aging using indices designed to predict chronological aging, phenotypic aging, and mortality risk, as well as a newly developed DNA methylation-based measure of telomere length. Using a sample of 500 African American middle aged smokers and non-smokers, we found that a) self-reported cigarette consumption was associated with accelerated intrinsic DNA methylation-based aging on some but not all DNA methylation-based aging indices, b) for those aging outcomes associated with self-reported cigarette consumption, DNA methylation-based indicators of smoking typically accounted for greater variance than did self-reported cigarette consumption, and c) self-reported cigarette consumption effects on DNA methylation-based aging indices typically were fully mediated by DNA methylation-based indicators of smoking (e.g., PACKYRS from GrimAge; or cg05575921 CpG site). Results suggest that when DNA methylation-based indices of smoking are substituted for self-reported assessments of smoking, they will typically fully reflect the varied impact of cigarette smoking on intrinsic, accelerated DNA methylation-based aging.

SUBMITTER: Lei MK

PROVIDER: S-EPMC7140795 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Effect of Tobacco Smoking Differs across Indices of DNA Methylation-Based Aging in an African American Sample: DNA Methylation-Based Indices of Smoking Capture These Effects.

Lei Man-Kit MK Gibbons Frederick X FX Simons Ronald L RL Philibert Robert A RA Beach Steven R H SRH

Genes 20200314 3

Smoking is one of the leading preventable causes of morbidity and mortality worldwide, prompting interest in its association with DNA methylation-based measures of biological aging. Considerable progress has been made in developing DNA methylation-based measures that correspond to self-reported smoking status. In addition, assessment of DNA methylation-based aging has been expanded to better capture individual differences in risk for morbidity and mortality. Untested to date, however, is whether ...[more]

PMID: 32183340

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Project description:BackgroundWhile smoking is known to associate with development of multiple diseases, the underlying mechanisms are still poorly understood. Tobacco smoking can modify the chemical integrity of DNA leading to changes in transcriptional activity, partly through an altered epigenetic state. We aimed to investigate the impact of smoking on lung cells collected from bronchoalveolar lavage (BAL).MethodsWe profiled changes in DNA methylation (5mC) and its oxidised form hydroxymethylation (5hmC) using conventional bisulphite (BS) treatment and oxidative bisulphite treatment with Illumina Infinium MethylationEPIC BeadChip, and examined gene expression by RNA-seq in healthy smokers.FindingsWe identified 1667 total 5mC + 5hmC, 1756 5mC and 67 5hmC differentially methylated positions (DMPs) between smokers and non-smokers (FDR-adjusted P <.05, absolute Δβ >0.15). Both 5mC DMPs and to a lesser extent 5mC + 5hmC were predominantly hypomethylated. In contrast, almost all 5hmC DMPs were hypermethylated, supporting the hypothesis that smoking-associated oxidative stress can lead to DNA demethylation, via the established sequential oxidation of which 5hmC is the first step. While we confirmed differential methylation of previously reported smoking-associated 5mC + 5hmC CpGs using former generations of BeadChips in alveolar macrophages, the large majority of identified DMPs, 5mC + 5hmC (1639/1667), 5mC (1738/1756), and 5hmC (67/67), have not been previously reported. Most of these novel smoking-associating sites are specific to the EPIC BeadChip and, interestingly, many of them are associated to FANTOM5 enhancers. Transcriptional changes affecting 633 transcripts were consistent with DNA methylation profiles and converged to alteration of genes involved in migration, signalling and inflammatory response of immune cells.InterpretationCollectively, these findings suggest that tobacco smoke exposure epigenetically modifies BAL cells, possibly involving a continuous active demethylation and subsequent increased activity of inflammatory processes in the lungs. FUND: The study was supported by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Stockholm County Council (ALF), the King Gustav's and Queen Victoria's Freemasons' Foundation, Knut and Alice Wallenberg Foundation, Neuro Sweden, and the Swedish MS foundation.

Project description:Background While smoking is known to associate with development of multiple diseases, the underlying mechanisms are still poorly understood. Tobacco smoking can modify the chemical integrity of DNA leading to changes in transcriptional activity, partly through an altered epigenetic state. We aimed to investigate the impact of smoking on lung cells collected from bronchoalveolar lavage (BAL). Methods We profiled changes in DNA methylation (5mC) and its oxidized form hydroxymethylation (5hmC) using conventional bisulfite (BS) treatment and oxidative bisulfite treatment with Illumina Infinium MethylationEPIC BeadChip, and examined gene expression by RNA-seq in healthy smokers. Findings We identified 1,667 BS methyl (5mC+5hmC), 1,756 5mC and 67 5hmC differentially methylated positions (DMPs) between smokers and nonsmokers (FDR <0.05, absolute Δβ >0.15). Both 5mC DMPs and to a lesser extent BS methyl (5mC+5hmC) were predominantly hypomethylated. In contrast, almost all 5hmC DMPs were hypermethylated, supporting the hypothesis that smoking-associated oxidative stress can lead to DNA demethylation, via the established sequential oxidation of which 5hmC is the first step. While we confirmed differential methylation of previously reported smoking-associated BS methyl CpGs using former generations of BeadChips in alveolar macrophages, the large majority of identified DMPs, BS methyl (1,639/1,667), 5mC (1,738/1,756), and 5hmC (67/67), have not been previously reported. Most of these novel smoking-associating sites are specific to the EPIC BeadChip and, interestingly, many of them are associated to FANTOM5 enhancers. Transcriptional changes affecting 633 transcripts were consistent with DNA methylation profiles and converged to alteration of genes involved in migration, signaling and inflammatory response of immune cells. Interpretation Collectively, these findings suggest that tobacco smoke exposure epigenetically modifies BAL cells, possibly involving a continuous active demethylation and subsequent increased activity of inflammatory processes in the lungs. -

Dataset Information

The Effect of Tobacco Smoking Differs across Indices of DNA Methylation-Based Aging in an African American Sample: DNA Methylation-Based Indices of Smoking Capture These Effects.

Publications

The Effect of Tobacco Smoking Differs across Indices of DNA Methylation-Based Aging in an African American Sample: DNA Methylation-Based Indices of Smoking Capture These Effects.

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