scholarly journals EpiSmokEr: A robust classifier to determine smoking status from DNA methylation data

2018 ◽  
Author(s):  
Sailalitha Bollepalli ◽  
Tellervo Korhonen ◽  
Jaakko Kaprio ◽  
Miina Ollikainen ◽  
Simon Anders

AbstractSelf-reported smoking status is prone to misclassification due to under-reporting, while biomarkers like cotinine can only measure recent exposure. Smoking strongly influences DNA methylation, with current, former and never smokers exhibiting different methylation profiles. Recently, two approaches were proposed to calculate scores based on smoking-responsive DNA methylation loci, to serve as reliable indicators of long-term exposure and potential biomarkers to estimate smoking behavior. However, these two methodologies need significant improvements to make them globally applicable to all populations and to achieve an optimal classification of individuals with unknown smoking habits. To advance the practical applicability of the smoking-associated methylation signals, we used machine learning methodology to train a classifier for smoking status prediction. We show the prediction performance of our classifier on three independent whole-blood test datasets demonstrating its robustness and global applicability. Furthermore, we show the cross-tissue functionality of our classifier in tissues other than blood. Additionally, we provide the community with an R package, EpiSmokEr, facilitating implementation of our classifier to predict smoking status in future studies.

Epigenomics ◽  
2019 ◽  
Vol 11 (13) ◽  
pp. 1469-1486 ◽  
Author(s):  
Sailalitha Bollepalli ◽  
Tellervo Korhonen ◽  
Jaakko Kaprio ◽  
Simon Anders ◽  
Miina Ollikainen

Aim: Smoking strongly influences DNA methylation, with current and never smokers exhibiting different methylation profiles. Methods: To advance the practical applicability of the smoking-associated methylation signals, we used machine learning methodology to train a classifier for smoking status prediction. Results: We show the prediction performance of our classifier on three independent whole-blood datasets demonstrating its robustness and global applicability. Furthermore, we examine the reasons for biologically meaningful misclassifications through comprehensive phenotypic evaluation. Conclusion: The major contribution of our classifier is its global applicability without a need for users to determine a threshold value for each dataset to predict the smoking status. We provide an R package, EpiSmokEr (Epigenetic Smoking status Estimator), facilitating the use of our classifier to predict smoking status in future studies.


2005 ◽  
Vol 20 (5-6) ◽  
pp. 431-441 ◽  
Author(s):  
B. Le Foll ◽  
P. Melihan-Cheinin ◽  
G. Rostoker ◽  
G. Lagrue ◽  

AbstractTobacco use is the leading preventable cause of death in developed countries. Millions of smokers are willing to stop, but few of them are able to do so. Clinicians should only use approaches that have demonstrated their efficacy in helping patients to stop smoking. This article summarizes the evidence-based major findings and clinical recommendations for the treatment of tobacco dependence of the French Health Products Safety Agency (AFSSAPS). Clinicians should enquire about the smoking status of each patient and provide information about health consequence of smoking and effective treatments available. These treatments include counseling (mainly individual or social support and behavioral and cognitive therapy) and pharmacological treatment with either nicotine replacement therapy (NRT) or bupropion LP. Pharmacological treatments should be used only for proven nicotine dependence, as assessed by the Fagerstrom test for Nicotine Dependence. The choice of pharmacologic treatment depends of the patient's preference and history and of the presence of contra-indications. The clinician should start with a single agent, but these treatments may be used in combination. Smoking behavior is a chronic problem that requires long-term management and follow-up. Access to intensive treatment combining pharmacological treatment and extensive behavioral and cognitive therapy should be available for highly dependent patients.


Author(s):  
Laurie Chassin ◽  
Clark C. Presson ◽  
Jonathan T. Macy ◽  
Steven J. Sherman

In this chapter, findings from a long-term, cohort-sequential, multigenerational study of cigarette smoking are used to illustrate the importance of a developmental approach for (1) understanding trajectories of smoking behavior (in relation to other forms of tobacco use) and the conditions and challenges of the developmental periods that show transitions in smoking status (particularly adolescent smoking onset and challenges for parents with adolescent children), (2) understanding heterogeneity in these trajectories because differing trajectories may have different etiological underpinnings as well as different implications for the intergenerational transmission of smoking, (3) recognizing that development unfolds within the larger context of societal and historical change and that societal change can influence outcomes, and (4) considering development within a family systems and multigenerational context.


Heart ◽  
2021 ◽  
pp. heartjnl-2021-318972
Author(s):  
Xiaowen Wang ◽  
Jia-Yi Dong ◽  
Renzhe Cui ◽  
Isao Muraki ◽  
Kokoro Shirai ◽  
...  

ObjectiveTo examine whether the relationship between smoking cessation and risk of cardiovascular disease (CVD) was modified by weight gain.MethodsA total of 69 910 participants (29 650 men and 46 260 women) aged 45–74 years were grouped into six groups by smoking status in the first and 5-year surveys: sustained smokers, recent quitters according to postcessation weight gain (no weight gain, 0.1–5.0 kg, >5.0 kg), long-term quitters and never smokers. Quitting smoking within and longer than 5 years were defined as recent and long-term quitters, respectively. We used Cox proportional hazard models to estimate the HR for incident CVD, coronary heart disease (CHD) and stroke.ResultsWe identified 4023 CVDs (889 CHDs and 3217 strokes) during a median of 14.8 years of follow-up. Compared with sustained smokers, the multivariable HR (95% CI) for CVD was 0.66 (0.52 to 0.83) for recent quitters without weight gain, 0.71 (0.55 to 0.90) for recent quitters with weight gain of 0.1–5.0 kg, 0.70 (0.44 to 1.10) for recent quitters with weight gain of >5.0 kg, 0.56 (0.49 to 0.64) for long-term quitters, and 0.60 (0.55 to 0.66) for never smokers. The analysis restricted to men showed a similar association. Prespecified analysis by age suggested that recent quitters overall had a lower HR for CVD among those aged <60 years vs ≥60 years. Similar patterns of association were observed in CHD and stroke.ConclusionsPostcessation weight gain did not attenuate the protective association between smoking cessation and risk of CVD.


Author(s):  
Ai Hori ◽  
Yosuke Inoue ◽  
Keisuke Kuwahara ◽  
Naoki Kunugita ◽  
Shamima Akter ◽  
...  

Abstract Background Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan. Methods We followed 70 896 workers aged 20–59 years (60 133 males, 10 763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (ie, SL lasting ≥30 consecutive days). Cause-specific analyses were also conducted. Results A total of 1777 people took long-term SL during a follow-up of 307 749 person years. Compared with never-smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.32; 95% confidence interval [CI] = 1.19 to 1.48). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.44, 95% CI = 1.22 to 1.69), cancer (HR = 1.49, 95% CI = 1.10 to 2.01), cardiovascular disease (CVD; HR = 2.16, 95% CI = 1.31 to 3.55), and injuries/external causes (HR = 1.83, 95% CI = 1.31 to 2.58). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.38, 95% CI = 0.99 to 1.92). Low-intensity smoking (ie, 1–10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to injuries/external causes compared with never-smokers. Conclusion In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term SL. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan. Implications Our study contributes to the literature on the association between smoking and SL in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on SL given that there is growing evidence of an elevated health risk associated with low-intensity smoking.


2018 ◽  
Vol 10 (2) ◽  
pp. 123-7
Author(s):  
Erika Diana Risanti ◽  
Aditya Kurniawan ◽  
Laila Wahyuningsih ◽  
Ery Kus Dwianingsih ◽  
Hanggoro Tri Rinonce ◽  
...  

BACKGROUND: Hypermethylation of RASSF1A and CDKN2A is one of epigenetic factor underlies nasopharyngeal carcinoma (NPC) development. Smoking behavior as an NPC’s risk factor causes aberrant DNA methylation. RASSF1A and CDKN2A promoter hypermethylation from peripheral blood cells correlates with smoking behavior. The use of body fluids including peripheral blood as a specimen for DNA methylation analyzes are widely developed, as less invasive method compared to the use of tissue biopsy. This study aims to observe the association between RASSF1A and CDKN2A methylation in peripheral blood and smoking behavioramong NPC patients.METHODS: Newly diagnosed NPC subjects were recruited from ear-nose-throat (ENT) outpatient clinic of Dr. Sardjito Hospital, Yogyakarta. DNA from buffycoat of 19 smokers and 20 non-smokers NPC’s patients were isolated. Bisulphite modification was applied to 500 ng of the isolated DNA. The methylation status was detected by MSP (methylation-specific polymerase chain reaction (PCR)). The association between smoking status and promoter hypermethylation was analysis using Chi-Square test.RESULTS: MSP analysis of RASSF1A showed that 68.42% smoker and 75% non-smoker NPC’s patients were methylated. MSP analysis of CDKN2A showed that 21.05% smoker and 25% non-smoker NPC’s patients were methylated. There was no association between smoking behavior with RASSF1A and CDKN2A methylation (p>0.05).CONCLUSION: Statistical analysis showed that smoking behavior is not associated with methylation of RASSF1A and CDKN2A among NPC’s patients.KEYWORDS: DNA methylation, CDKN2A, RASSF1A, Nasopharyngeal carcinoma, Smoking


2021 ◽  
Author(s):  
Sharon Cox ◽  
Jamie Brown ◽  
Loren Kock ◽  
Lion Shahab

Abstract Introduction: Up-to-date monitoring of non-combustible nicotine products (NNP) is important to assess their impact. To date, there is little evidence on the association between long-term regular use (defined here as one-year or more) of NNP and current smoking status. Aims/methods: The purpose of this study was to examine the prevalence, and sociodemographic, alcohol and smoking status correlates, of ever regular use of NNP in England in 2020.A cross sectional survey of adults in England between February and June 2020. Results: 8,486 adults were surveyed, 94.9% (8,055) were complete cases. The weighted prevalence of ever regular NNP use was 5.4% (n=436; 95%CI 5.0-6.0), of which 82% (n=360; 95%CI 78.7-85.8) was single, and 18% (n=79; 95%CI 14.8-22) multiple product use. Amongst ever regular NNP users, the prevalence of ever regular nicotine replacement therapies (NRT), e-cigarette and heated tobacco product use was 64.7% (95% CI 60.1-69), 43.4% (95%CI 38.8-48) and 2.5% (95% CI 1.4-4.5), respectively. In regression analysis, ever regular NNP use was independently associated with smoking status, being significantly higher among current (22.3%; Adjusted OR (aOR) 34.9, 95%CI 24.0-50.8) and ex-smokers (12.7%, aOR 19.8, 95%CI 11.1-14.4) than among never smokers (0.6%). More advantaged occupational grade (aOR, 1.27 95% CI 1.02-1.57) and at least hazardous alcohol use (aOR, 1.38 95%CI 1.06-1.78) were independently associated with greater prevalence of ever regular NNP use.Conclusions: Ever regularly using NNP was highest among smokers and ex-smokers and rare among never smokers. Among people who have ever regularly used NNP, NRT is the most popular.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 668-668
Author(s):  
Jonah Fisher ◽  
Helen Meier ◽  
Jessica Faul ◽  
Colter Mitchell ◽  
Eileen Crimmins ◽  
...  

Abstract DNA methylation (DNAm) is an increasingly popular biomarker of health and aging outcomes. Smoking behaviors have a significant and well documented correlation with methylation signatures within the epigenome and are important confounding variables to account for in epigenome-wide association studies (EWAS). However, the common classification of individuals as ‘current’, ‘former’, and ‘never’ smokers may miss crucial DNAm patterns associated with other smoking behaviors such as duration, intensity, and frequency of cigarette smoking, resulting in an underestimation of the contribution of smoking behaviors to DNAm and potentially biasing EWAS results. We investigated associations between multiple smoking behavioral phenotypes (smoking pack years, smoking duration, smoking start age, and smoking end age) and single site DNAm using linear regressions adjusting for age, sex, race/ethnicity, education, and cell-type proportions in a subsample of individuals who participated in the HRS 2016 Venous Blood Study (N=1,775). DNAm was measured using the Infinium Methylation EPIC BeadChip. All 4 phenotypes had significant associations (FDR &lt; 0.05) with many methylation sites (packyears=6859, smoking duration=6572, start age=11374, quit age=773). There was not much overlap in DNAm sites between the full set of models with only 6 overlapping between all 4. However, the phenotypes packyears and smoking duration showed large overlap (N=3782). Results suggest additional smoking phenotypes beyond current/former/never smoker classification should be included in EWAS analyses to appropriately account for the influence of smoking behaviors on DNAm.


2020 ◽  
Vol 8 (1) ◽  
pp. e001249
Author(s):  
Jae Woo Choi ◽  
Euna Han ◽  
Tae Hyun Kim

IntroductionThis study aimed to examine the association between smoking cessation after new-onset type 2 diabetes and overall and cause-specific mortality risks among Korean men.Research design and methodsThe Korean National Health Insurance Service-National Health Screening Cohort database was searched, and 13 377 Korean men aged ≥40 years diagnosed with new-onset type 2 diabetes between 2004 and 2007 were included and followed up until 2013. We defined smoking status changes by comparing participants’ answers in the last survey before diagnosis to those in the first survey after diagnosis. We estimated the adjusted HR (AHR) and 95% CI for mortality risk using multivariable Cox proportional hazards regression models.ResultsWe identified 1014 all-cause mortality events (cancer, n=406 and cardiovascular disease (CVD), n=184) during an average follow-up duration of 7.2 years. After adjustment for all confounding factors, the reduced risk of all-cause mortality was more significant among short-term quitters (AHR 0.78; 95% CI 0.64 to 0.95), long-term quitters (AHR 0.68; 95% CI 0.54 to 0.85), and never smokers (AHR 0.66; 95% CI 0.56 to 0.78) compared with current smokers (p for trend <0.001). The lower risk of mortality from cancer was significant among the short-term quitters (AHR 0.60; 95% CI 0.44 to 0.83), long-term quitters (AHR 0.67; 95% CI 0.46 to 0.90), and never smokers (AHR 0.50; 95% CI 0.39 to 0.65) compared with current smokers (p for trend <0.001). There was no significant association between changes in smoking status and death from CVD. Smoking cessation after diagnosis in non-obese individuals (AHR 0.73; 95% CI 0.58 to 0.92) and exercisers (AHR 0.54; 95% CI 0.38 to 0.76) was significantly associated with reduced mortality risk than current smoking.ConclusionsSmoking cessation after new-onset type 2 diabetes was associated with reduced mortality risk.


Author(s):  
Qing Wang ◽  
John Rizzo ◽  
Hai Fang

Background: Evidence suggests that following major individual health shocks, smokers change their smoking behaviors. However, little is known about the association between spousal health shocks and smoking. This study examined the contemporaneous and long-term effects of individual and spousal health shocks on males’ smoking behaviors in China. Methods: This study employed a nation-wide data base from the 1991–2011 China Health and Nutrition Study. Random effects models were estimated to ascertain the impacts of health shocks on males’ smoking behavior. Smoking behaviors were measured by smoking status, smoking consumption and smoking cessation. Results: In the short term, respondents who incurred health shocks decreased their likelihood of smoking by 10%. In addition, health shocks decreased the likelihood of heavy smoking versus the combined moderate and light categories by 41.6%, and increased their likelihood of quitting by 85.3% for ever smokers. Spousal health shocks had no significant effects on individual smoking behaviors. The long-term effects were similar to the short term impacts. Conclusions: People changed their smoking behaviors in response to their own health experiences but not those of their spouses. Antismoking messages about the health effects on others are unlikely to influence individual smoking behaviors, unless individuals believed that they are personally vulnerable to smoking-related diseases.


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