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Hermann Brenner - One of the best experts on this subject based on the ideXlab platform.
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Smoking-associated DNA methylation markers predict lung cancer incidence
Clinical epigenetics, 2016Co-Authors: Yan Zhang, Ben Schöttker, Bernd Holleczek, Magdeldin Elgizouli, Alexandra Nieters, Hermann BrennerAbstract:Newly established blood DNA methylation markers that are strongly associated with smoking might open new avenues for lung cancer (LC) screening. We aimed to assess the performance of the top hits from previous epigenome-wide association studies in prediction of LC incidence. In a prospective nested case-control study, DNA methylation at AHRR (cg05575921), 6p21.33 (cg06126421), and F2RL3 (cg03636183) were measured by pyrosequencing in baseline whole blood samples of 143 incident LC cases identified during 11 years of follow-up and 457 age- and sex-matched controls without diagnosis of LC until the end of follow-up. The individual and joint associations of the 3 markers with LC risk were estimated by logistic regression, adjusted for potential confounders including smoking status and cigarette pack-years. The predictive performance was evaluated for both the individual markers and their combinations derived from multiple algorithms. Pronounced demethylation of all 3 markers was observed at baseline among cases compared to controls. Risk of developing LC increased with decreasing DNA methylation levels, with adjusted ORs (95% CI) of 15.86 (4.18–60.17), 8.12 (2.69–4.48), and 10.55 (3.44–32.31), respectively, for participants in the lowest quartile of AHRR, 6p21.33, and F2RL3 compared to participants in the highest 2 quartiles of each site among controls. The individual 3 markers exhibited similar accuracy in predicting LC incidence, with AUCs ranging from 0.79 to 0.81. Combination of the 3 markers did not improve the predictive performance (AUC = 0.80). The individual markers or their combination outperformed self-reported smoking exposure particularly in light smokers. No variation in risk prediction was identified with respect to age, follow-up time, and histological subtypes. AHRR, 6p21.33, and F2RL3 methylation in blood DNA are predictive for LC development, which might be useful for identification of risk groups for further specific screening, such as CT examination.
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dna methylation changes of whole blood cells in response to active smoking exposure in adults a systematic review of dna methylation studies
Clinical Epigenetics, 2015Co-Authors: Xu Gao, Lutz P. Breitling, Min Jia, Yanyan Zhang, Hermann BrennerAbstract:Active smoking is a major preventable public health problem and an established critical factor for epigenetic modification. In this systematic review, we identified 17 studies addressing the association of active smoking exposure with methylation modifications in blood DNA, including 14 recent epigenome-wide association studies (EWASs) and 3 gene-specific methylation studies (GSMSs) on the gene regions identified by EWASs. Overall, 1460 smoking-associated CpG sites were identified in the EWASs, of which 62 sites were detected in multiple (≥3) studies. The three most frequently reported CpG sites (genes) in whole blood samples were cg05575921 (AHRR), cg03636183 (F2RL3), and cg19859270 (GPR15), followed by other loci within intergenic regions 2q37.1 and 6p21.33. These significant smoking-related genes were further assessed by specific methylation assays in three GSMSs and reflected not only current but also lifetime or long-term exposure to active smoking. In conclusion, this review summarizes the evidences for the use of blood DNA methylation patterns as biomarkers of smoking exposure for research and clinical practice. In particular, it provides a reservoir for constructing a smoking exposure index score which could be used to more precisely quantify long-term smoking exposure and evaluate the risks of smoking-induced diseases.
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F2RL3 methylation, lung cancer incidence and mortality.
International journal of cancer, 2015Co-Authors: Yan Zhang, Ben Schöttker, José M Ordóñez-mena, Bernd Holleczek, Rongxi Yang, Barbara Burwinkel, Katja Butterbach, Hermann BrennerAbstract:© 2015 UICC.Smoking accounts for a large share of lung cancer. F2RL3 methylation was recently identified as a biomarker closely reflecting both current and past smoking exposure. We aimed to assess the associations of F2RL3 methylation with lung cancer incidence and mortality. In a large population-based cohort study, F2RL3 methylation was measured in baseline blood samples of 4,987 participants by MassARRAY. Associations of F2RL3 methylation and smoking with lung cancer incidence/mortality during a median follow-up of 10.9 years were assessed by Cox regression, controlling for potential confounders. The ability of F2RL3 methylation to predict lung cancer was examined by Harrell's C statistics. Hypomethylation at F2RL3 was strongly associated with both lung cancer incidence and mortality, with age- and sex-adjusted hazard ratios (HR; 95% CI) of 9.99 (5.61-17.79) and 16.86 (8.53-33.34), respectively, for participants whose methylation intensity were ≤0.54 compared with whose methylation intensity were ≥0.75. Strongly elevated HRs of 2.88 (1.42-5.84) and 5.17 (2.28-11.70) persisted even after controlling for multiple covariates including smoking status and pack-years. With fully adjusted HRs of 9.92 (2.88-34.12) and 16.48 (4.10-66.15), the associations between methylation and the two outcomes were particularly strong among participants≥65 years. Combination of F2RL3 methylation and pack-years predicted lung cancer incidence with high accuracy (optimism-corrected Harrell's C statistics=0.86 for participants≥65 years). These findings suggested that F2RL3 methylation is a very strong predictor of lung cancer risk and mortality, particularly at older age. The potential implications of F2RL3 methylation for early detection, risk stratification and prevention of lung cancer warrant further exploration.
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F2RL3 methylation in blood DNA is a strong predictor of mortality
International journal of epidemiology, 2014Co-Authors: Yan Zhang, Ben Schöttker, Bernd Holleczek, Rongxi Yang, Barbara Burwinkel, Lutz P. Breitling, Hermann BrennerAbstract:Background: Smoking is a major cause of morbidity and mortality. Smoking-related epigenetic biomarkers may open new avenues to better quantify the adverse health effects of smoking, and to better understanding of the underlying mechanisms. We aimed to evaluate the clinical implications of F2RL3 methylation, a novel epigenetic biomarker of smoking exposure disclosed by recent genome-wide methylation studies. Methods: Blood DNA methylation at F2RL3 (also known as PAR-4) was quantified in baseline samples of 3588 participants aged 50‐75 years in a large population-based prospective cohort study by MALDI-TOF mass spectrometry. Deaths were recorded during a median follow-up of 10.1 years. The associations of methylation intensity and of smoking with all-cause, cardiovascular, cancer and other mortality were assessed by Cox’s proportional hazards regression, controlling for potential confounding factors. Results: Lower methylation intensity at F2RL3 was strongly associated with mortality. After adjustment for multiple covariates including smoking, hazard ratios [95% confidence interval (CI)] for death from any cause, cardiovascular disease, cancer or other causes were 2.60 (95% CI, 1.81-3.74), 2.45 (95% CI, 1.28-4.68), 2.94 (95% CI, 1.68-5.14) and 2.39 (95% CI, 1.11-5.16), respectively, in subjects in the lowest quartile of methylation intensity compared with subjects in the highest quartile. The associations with mortality outcomes were much stronger among men than among women. In addition, strong positive associations of smoking with each of the outcomes were substantially weakened, and almost disappeared when controlling for F2RL3 methylation intensity. Conclusions: F2RL3 methylation is a strong predictor of mortality, including all-cause, cardiovascular, cancer and other mortality. Systemic adverse effects of smoking may be mediated by pathways associated with F2RL3 methylation.
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F2RL3 methylation as a biomarker of current and lifetime smoking exposures.
Environmental health perspectives, 2013Co-Authors: Yan Zhang, Rongxi Yang, Barbara Burwinkel, Lutz P. Breitling, Hermann BrennerAbstract:Background: Recent genome-wide DNA methylation studies have found a pronounced difference in methylation of the F2RL3 gene (also known as PAR-4) in blood DNA according to smoking exposure. Knowledg...
Karin Broberg - One of the best experts on this subject based on the ideXlab platform.
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Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
Occupational and environmental medicine, 2020Co-Authors: Ayman Alhamdow, Håkan Tinnerberg, Maria Albin, Christian H. Lindh, Jessika Hagberg, Pål Graff, Annette M. Krais, Per Gustavsson, Yona J. Essig, Karin BrobergAbstract:Objectives Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. Methods We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation of F2RL3 and AHRR using pyrosequencing. Results Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p Conclusions Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation of F2RL3 and AHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.
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Filaggrin variations are associated with PAH metabolites in urine and DNA alterations in blood.
Environmental research, 2019Co-Authors: Karin Wahlberg, Håkan Tinnerberg, Maria Albin, Ayman Alhamdow, Christian H. Lindh, Emelie Rietz Liljedahl, Carola Lidén, Karin BrobergAbstract:Abstract Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment.
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DNA methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons.
Carcinogenesis, 2018Co-Authors: Ayman Alhamdow, Håkan Tinnerberg, Maria Albin, Christian H. Lindh, Jessika Hagberg, Pål Graff, Håkan Westberg, Annette M. Krais, Per Gustavsson, Karin BrobergAbstract:Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1 and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B = -2.04; P < 0.057, adjusted for smoking and age) and lower average AHRR methylation (B = -2.05; P < 0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B = -0.81; P < 0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.
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Exposure to welding fumes is associated with hypomethylation of the F2RL3 gene: a cardiovascular disease marker.
Occupational and environmental medicine, 2015Co-Authors: Mohammad Bakhtiar Hossain, Maria Hedmer, Håkan Tinnerberg, Maria Albin, Karin BrobergAbstract:Background Welders are at risk for cardiovascular disease. Recent studies linked tobacco smoke exposure to hypomethylation of the F2RL3 (coagulation factor II (thrombin) receptor-like 3) gene, a marker for cardiovascular disease prognosis and mortality. However, whether welding fumes cause hypomethylation of F2RL3 remains unknown. Methods We investigated 101 welders (median span of working as a welder: 7 years) and 127 unexposed controls (non-welders with no obvious exposure to respirable dust at work), age range 23–60 years, all currently non-smoking, in Sweden. The participants were interviewed about their work history, lifestyle factors and diseases. Personal sampling of respirable dust was performed for the welders. DNA methylation of F2RL3 in blood was assessed by pyrosequencing of four CpG sites, CpG_2 (corresponds to cg03636183) to CpG_5, in F2RL3 . Multivariable linear regression analysis was used to assess the association between exposure to welding fumes and F2RL3 methylation. Results Welders had 2.6% lower methylation of CpG_5 than controls (p F2RL3 (CpG_2, CpG_4 and CpG_5) compared to never-smokers. A non-significant lower risk of cardiovascular disease with more methylation was observed for all CpG sites. Conclusions Welding fumes exposure and previous smoking were associated with F2RL3 hypomethylation. This finding links low-to-moderate exposure to welding fumes to adverse effects on the cardiovascular system, and suggests a potential mechanistic pathway for this link, via epigenetic effects on F2RL3 expression.
Lutz P. Breitling - One of the best experts on this subject based on the ideXlab platform.
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dna methylation changes of whole blood cells in response to active smoking exposure in adults a systematic review of dna methylation studies
Clinical Epigenetics, 2015Co-Authors: Xu Gao, Lutz P. Breitling, Min Jia, Yanyan Zhang, Hermann BrennerAbstract:Active smoking is a major preventable public health problem and an established critical factor for epigenetic modification. In this systematic review, we identified 17 studies addressing the association of active smoking exposure with methylation modifications in blood DNA, including 14 recent epigenome-wide association studies (EWASs) and 3 gene-specific methylation studies (GSMSs) on the gene regions identified by EWASs. Overall, 1460 smoking-associated CpG sites were identified in the EWASs, of which 62 sites were detected in multiple (≥3) studies. The three most frequently reported CpG sites (genes) in whole blood samples were cg05575921 (AHRR), cg03636183 (F2RL3), and cg19859270 (GPR15), followed by other loci within intergenic regions 2q37.1 and 6p21.33. These significant smoking-related genes were further assessed by specific methylation assays in three GSMSs and reflected not only current but also lifetime or long-term exposure to active smoking. In conclusion, this review summarizes the evidences for the use of blood DNA methylation patterns as biomarkers of smoking exposure for research and clinical practice. In particular, it provides a reservoir for constructing a smoking exposure index score which could be used to more precisely quantify long-term smoking exposure and evaluate the risks of smoking-induced diseases.
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F2RL3 methylation in blood DNA is a strong predictor of mortality
International journal of epidemiology, 2014Co-Authors: Yan Zhang, Ben Schöttker, Bernd Holleczek, Rongxi Yang, Barbara Burwinkel, Lutz P. Breitling, Hermann BrennerAbstract:Background: Smoking is a major cause of morbidity and mortality. Smoking-related epigenetic biomarkers may open new avenues to better quantify the adverse health effects of smoking, and to better understanding of the underlying mechanisms. We aimed to evaluate the clinical implications of F2RL3 methylation, a novel epigenetic biomarker of smoking exposure disclosed by recent genome-wide methylation studies. Methods: Blood DNA methylation at F2RL3 (also known as PAR-4) was quantified in baseline samples of 3588 participants aged 50‐75 years in a large population-based prospective cohort study by MALDI-TOF mass spectrometry. Deaths were recorded during a median follow-up of 10.1 years. The associations of methylation intensity and of smoking with all-cause, cardiovascular, cancer and other mortality were assessed by Cox’s proportional hazards regression, controlling for potential confounding factors. Results: Lower methylation intensity at F2RL3 was strongly associated with mortality. After adjustment for multiple covariates including smoking, hazard ratios [95% confidence interval (CI)] for death from any cause, cardiovascular disease, cancer or other causes were 2.60 (95% CI, 1.81-3.74), 2.45 (95% CI, 1.28-4.68), 2.94 (95% CI, 1.68-5.14) and 2.39 (95% CI, 1.11-5.16), respectively, in subjects in the lowest quartile of methylation intensity compared with subjects in the highest quartile. The associations with mortality outcomes were much stronger among men than among women. In addition, strong positive associations of smoking with each of the outcomes were substantially weakened, and almost disappeared when controlling for F2RL3 methylation intensity. Conclusions: F2RL3 methylation is a strong predictor of mortality, including all-cause, cardiovascular, cancer and other mortality. Systemic adverse effects of smoking may be mediated by pathways associated with F2RL3 methylation.
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F2RL3 methylation as a biomarker of current and lifetime smoking exposures.
Environmental health perspectives, 2013Co-Authors: Yan Zhang, Rongxi Yang, Barbara Burwinkel, Lutz P. Breitling, Hermann BrennerAbstract:Background: Recent genome-wide DNA methylation studies have found a pronounced difference in methylation of the F2RL3 gene (also known as PAR-4) in blood DNA according to smoking exposure. Knowledg...
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Current Genetics and Epigenetics of Smoking/Tobacco-Related Cardiovascular Disease
Arteriosclerosis thrombosis and vascular biology, 2013Co-Authors: Lutz P. BreitlingAbstract:Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns. This could render the genetics and epigenetics of smoking-related cardiovascular disease a textbook example of environmental epigenetics and modern approaches to multimodal data analysis. A pronounced association of smoking-related methylation patterns in the F2RL3 gene with prognosis in patients with stable coronary heart disease has recently been described. Nonetheless, surprisingly little concrete knowledge on the role of specific genetic variants and epigenetic modifications in the development of cardiovascular diseases in people who smoke has been accumulated. Beyond the current knowledge, the present review briefly outlines some chief challenges and priorities for moving forward in this field.
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Smoking, F2RL3 methylation, and prognosis in stable coronary heart disease
European heart journal, 2012Co-Authors: Lutz P. Breitling, Barbara Burwinkel, Katrin Salzmann, Dietrich Rothenbacher, Hermann BrennerAbstract:Aims In a recent genome-wide study, cytosine bases in the F2RL3 gene, which codes for a protein relevant for cardiovascular physiology, were discovered to be hypomethylated in smokers. We aimed to determine the clinical importance of methylation at the F2RL3 locus. Methods and results In the KAROLA prospective cohort study, 1206 participants of inpatient cardiovascular rehabilitation programmes after experiencing an acute coronary syndrome, myocardial infarction, or coronary intervention were recruited in two clinics in Germany. Active follow-up was conducted over 8 years. Methylation at loci in F2RL3 was characterized by Sequenom matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations of methylation and smoking with secondary cardiovascular events, and cause-specific and all-cause mortality were examined by multiple Cox's regression estimating confounder-controlled hazard ratios. A total of 49 non-fatal myocardial infarctions, 41 non-fatal strokes, 64 cardiovascular deaths, and 50 deaths due to other causes were observed. In Cox's models controlling for established prognostic factors, F2RL3 methylation was strongly associated with mortality. Adjusted hazard ratios (95% confidence intervals) for death from cardiovascular, non-cardiovascular, or any cause were 2.32 (0.97–5.58), 5.16 (1.81–14.7), and 3.19 (1.64–6.21) in subjects in the lowest quartile of methylation in comparison to the highest quartile. In contrast, no association was seen with the combined secondary event outcome. The strong association of smoking with all outcomes was markedly attenuated when F2RL3 was included in the regression models. Conclusion The results seem to indicate methylation in F2RL3 to be a potential mediator of the detrimental impact of smoking and to be strongly related to mortality among patients with stable coronary heart disease. Multidisciplinary research efforts are needed to unravel prognostic, preventive, and therapeutic potentials of these pronounced associations.
Martin A. Kennedy - One of the best experts on this subject based on the ideXlab platform.
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Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort.
Translational psychiatry, 2020Co-Authors: Amy J. Osborne, John F. Pearson, Alexandra J Noble, Neil J. Gemmell, L. John Horwood, Joseph M. Boden, Miles C. Benton, Donia Macartney-coxson, Martin A. KennedyAbstract:Cannabis use is of increasing public health interest globally. Here we examined the effect of heavy cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study, CHDS). A total of 48 heavy cannabis users were selected from the CHDS cohort, on the basis of their adult exposure to cannabis and tobacco, and DNA methylation assessed from whole blood samples, collected at approximately age 28. Methylation in heavy cannabis users was assessed, relative to non-users (n = 48 controls) via the Illumina Infinium® MethylationEPIC BeadChip. We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level (P < 10-7). However, there were 521 sites differentially methylated at P < 0.001 which were enriched for genes involved in neuronal signalling (glutamatergic synapse and long-term potentiation) and cardiomyopathy. Further, the most differentially methylated loci were associated with genes with reported roles in brain function (e.g. TMEM190, MUC3L, CDC20 and SP9). We conclude that the effects of cannabis use on the mature human blood methylome differ from, and are less pronounced than, the effects of tobacco use, and that larger sample sizes are required to investigate this further.
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Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort
Translational Psychiatry, 2020Co-Authors: Amy J. Osborne, John F. Pearson, Alexandra J Noble, Neil J. Gemmell, L. John Horwood, Joseph M. Boden, Miles C. Benton, Donia Macartney-coxson, Martin A. KennedyAbstract:Cannabis use is of increasing public health interest globally. Here we examined the effect of heavy cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study, CHDS). A total of 48 heavy cannabis users were selected from the CHDS cohort, on the basis of their adult exposure to cannabis and tobacco, and DNA methylation assessed from whole blood samples, collected at approximately age 28. Methylation in heavy cannabis users was assessed, relative to non-users ( n = 48 controls) via the Illumina Infinium® MethylationEPIC BeadChip. We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level ( P
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Genome-wide DNA methylation analysis of heavy cannabis use in a New Zealand longitudinal cohort
2019Co-Authors: Amy J. Osborne, John F. Pearson, Alexandra J Noble, Neil J. Gemmell, L. John Horwood, Joseph M. Boden, Miles C. Benton, Donia Macartney-coxson, Martin A. KennedyAbstract:ABSTRACT Heavy, long term cannabis use is associated with an increased risk of adverse psychosocial outcomes, depression and schizophrenia. Here we examined the effect of cannabis use, with and without tobacco, on genome-wide DNA methylation in a longitudinal birth cohort (Christchurch Health and Development Study). We found the most differentially methylated sites in cannabis with tobacco users were in the AHRR and F2RL3 genes, replicating previous studies on the effects of tobacco. Cannabis-only users had no evidence of differential methylation in these genes, or at any other loci at the epigenome-wide significance level (P
Irina Lehmann - One of the best experts on this subject based on the ideXlab platform.
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Tobacco smoking differently influences cell types of the innate and adaptive immune system-indications from CpG site methylation.
Clinical epigenetics, 2016Co-Authors: Mario Bauer, Beate Fink, Gunda Herberth, Markus Eszlinger, Loreen Thürmann, Irina LehmannAbstract:Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86.7 and 93.3 %) in whole blood account for changes in granulocytes. Analyzing, in more detail, seven highly significant reported smoking-induced methylation changes at single CpGs in different blood cell types of healthy volunteers (n = 32), we confirmatively found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were significantly hypomethylated in granulocytes (-11.3 %, p = 0.001; -8.7 %, p = 0.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15 were found to be hypomethylated in PBMC (-4.3 %, p = 0.003; -4.2 %, P = 0.009, respectively) and their subtypes of GPR15 non-expressing (-3.2 %, p = 0.027; -2.5 %, p = 0.032, respectively) and smoking-evoked GPR15 expressing T cells (-15.8 %, p < 0.001; -13.8 %, p = 0.018, respectively) but not in granulocytes. In contrast, cg05575921 within AHRR was hypomethylated in every analyzed cell type of smokers, but with a different degree. Both, hypomethylation at cg05575921 in granulocytes (-55.2 % methylation change in smokers, p < 0.001) and the frequency of GPR15+ T cells (9.8-37.1 % in smokers), possessing a specific hypomethylation at cg19859270, were strongly associated with smoking behavior at individual level and could therefore serve as valuable biomarkers indicating a disturbed homeostasis in smokers. In contrast to the reported long-term persistent methylation changes in adult smokers after cessation, the hypomethylation at cg05575921 in prenatally tobacco smoke-exposed children (n = 13) from our LINA cohort was less stable and disappeared already within 2 years after birth. Studying cell type-specific methylation changes provides helpful information regarding the biological relevance of epigenetic modifications. Here, we could show that smoking differently affects both cells of the innate and adaptive immune systems.
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Tobacco smoking differently influences cell types of the innate and adaptive immune system—indications from CpG site methylation
Clinical Epigenetics, 2016Co-Authors: Mario Bauer, Beate Fink, Gunda Herberth, Markus Eszlinger, Loreen Thürmann, Irina LehmannAbstract:Background Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. Results Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86.7 and 93.3 %) in whole blood account for changes in granulocytes. Analyzing, in more detail, seven highly significant reported smoking-induced methylation changes at single CpGs in different blood cell types of healthy volunteers ( n = 32), we confirmatively found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were significantly hypomethylated in granulocytes (−11.3 %, p = 0.001; −8.7 %, p = 0.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15 were found to be hypomethylated in PBMC (−4.3 %, p = 0.003; −4.2 %, P = 0.009, respectively) and their subtypes of GPR15 non-expressing (−3.2 %, p = 0.027; −2.5 %, p = 0.032, respectively) and smoking-evoked GPR15 expressing T cells (−15.8 %, p
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Tobacco smoking differently influences cell types of the innate and adaptive immune system-indications from CpG site methylation.
Clinical Epigenetics, 2016Co-Authors: Mario Bauer, Beate Fink, Gunda Herberth, Markus Eszlinger, Loreen Thürmann, Irina LehmannAbstract:Tobacco smoke is worldwide one of the main preventable lifestyle inhalative pollutants causing severe adverse health effects. Epidemiological studies revealed association of tobacco smoking with epigenetic changes at single CpGs in blood. However, the biological relevance of the often only marginal methylation changes remains unclear. Comparing genome-wide changes in CpG methylation of three recently reported epidemiological datasets, two obtained on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes evident that the majority of methylation changes (86.7 and 93.3 %) in whole blood account for changes in granulocytes. Analyzing, in more detail, seven highly significant reported smoking-induced methylation changes at single CpGs in different blood cell types of healthy volunteers (n = 32), we confirmatively found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were significantly hypomethylated in granulocytes (−11.3 %, p = 0.001; −8.7 %, p = 0.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15 were found to be hypomethylated in PBMC (−4.3 %, p = 0.003; −4.2 %, P = 0.009, respectively) and their subtypes of GPR15 non-expressing (−3.2 %, p = 0.027; −2.5 %, p = 0.032, respectively) and smoking-evoked GPR15 expressing T cells (−15.8 %, p
