Epigenetic biomarkers for smoking cessation

Fang, Fang; Andersen, Allan M.; Philibert, Robert A.; Hancock, Dana B.

doi:10.1016/j.addicn.2023.100079

Cited by 8 publications

(5 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 49 , 50 Since smoking is a preventable cause of heart disease and reversion of aryl hydrocarbon receptor repressor methylation is a marker of smoking cessation, this marker could be used to not only help clinicians more exactly understand the pathogenesis of a given patient's CHD, but also could be reassessed as part of a more holistic precision epigenetic approach to smoking cessation and secondary CHD treatment. 51 …”

Section: Discussionmentioning

confidence: 99%

Validation of an Integrated Genetic‐Epigenetic Test for the Assessment of Coronary Heart Disease

Philibert,

Dogan,

Knight

et al. 2023

JAHA

Self Cite

View full text Add to dashboard Cite

Background Coronary heart disease (CHD) is the leading cause of death in the world. Unfortunately, many of the key diagnostic tools for CHD are insensitive, invasive, and costly; require significant specialized infrastructure investments; and do not provide information to guide postdiagnosis therapy. In prior work using data from the Framingham Heart Study, we provided in silico evidence that integrated genetic–epigenetic tools may provide a new avenue for assessing CHD. Methods and Results In this communication, we use an improved machine learning approach and data from 2 additional cohorts, totaling 449 cases and 2067 controls, to develop a better model for ascertaining symptomatic CHD. Using the DNA from the 2 new cohorts, we translate and validate the in silico findings into an artificial intelligence–guided, clinically implementable method that uses input from 6 methylation‐sensitive digital polymerase chain reaction and 10 genotyping assays. Using this method, the overall average area under the curve, sensitivity, and specificity in the 3 test cohorts is 82%, 79%, and 76%, respectively. Analysis of targeted cytosine‐phospho‐guanine loci shows that they map to key risk pathways involved in atherosclerosis that suggest specific therapeutic approaches. Conclusions We conclude that this scalable integrated genetic–epigenetic approach is useful for the diagnosis of symptomatic CHD, performs favorably as compared with many existing methods, and may provide personalized insight to CHD therapy. Furthermore, given the dynamic nature of DNA methylation and the ease of methylation‐sensitive digital polymerase chain reaction methodologies, these findings may pave a pathway for precision epigenetic approaches for monitoring CHD treatment response.

show abstract

Section: Discussionmentioning

confidence: 99%

Validation of an Integrated Genetic‐Epigenetic Test for the Assessment of Coronary Heart Disease

Philibert,

Dogan,

Knight

et al. 2023

JAHA

Self Cite

View full text Add to dashboard Cite

show abstract

“…This lack of a significant finding may be secondary to the short time scale of this study. There have been several epigenome-wide studies of the time dependency of methylation reversion in those undergoing smoking cessation [ 18 , 41 , 42 ]. These studies have demonstrated that the reversion of smoking-associated methylation changes in the thousands of CpG sites affected can be divided into three categories.…”

Section: Discussionmentioning

confidence: 99%

“…However, they were offered USD 400 for having biochemically verified smoking cessation at each of the three follow-up visits. Smoking cessation can take a variable course and self-reports of smoking can be unreliable [ 15 , 16 ]; therefore, smoking intensity at each visit was assessed using digital measures of cg05575921, a generally accepted measure of smoking intensity and smoking cessation [ 17 , 18 ]. At the time of the preparation of the sample, a total of 75 subjects had enrolled in the study, with 39 successfully attending all four clinic visits.…”

Section: Methodsmentioning

confidence: 99%

The Reversion of the Epigenetic Signature of Coronary Heart Disease in Response to Smoking Cessation

Philibert

Moody

Philibert

et al. 2023

Genes

Self Cite

View full text Add to dashboard Cite

Coronary heart disease (CHD) is the leading cause of death worldwide. However, current diagnostic tools for CHD, such as coronary computed tomography angiography (CCTA), are poorly suited for monitoring treatment response. Recently, we have introduced an artificial-intelligence-guided integrated genetic–epigenetic test for CHD whose core consists of six assays that determine methylation in pathways known to moderate the pathogenesis of CHD. However, whether methylation at these six loci is sufficiently dynamic to guide CHD treatment response is unknown. To test that hypothesis, we examined the relationship of changes in these six loci to changes in cg05575921, a generally accepted marker of smoking intensity, using DNA from a cohort of 39 subjects undergoing a 90-day smoking cessation intervention and methylation-sensitive digital PCR (MSdPCR). We found that changes in epigenetic smoking intensity were significantly associated with reversion of the CHD-associated methylation signature at five of the six MSdPCR predictor sites: cg03725309, cg12586707, cg04988978, cg17901584, and cg21161138. We conclude that methylation-based approaches could be a scalable method for assessing the clinical effectiveness of CHD interventions, and that further studies to understand the responsiveness of these epigenetic measures to other forms of CHD treatment are in order.

show abstract

“…ATS levels and MSdPCR assessment of cg07375256 levels were conducted using reagents and software from Behavioral Diagnostics (Coralville, IA) and from Bio-Rad (Hercules, CA) using our previously published methods [ 9 , 10 , 12 , 37 ]. Similarly, the smoking intensity at cg05575921, a generally accepted biomarker for smoking intensity [ 38 ], was assessed using reagents and software from Behavioral Diagnostics (Coralville, IA) and from Bio-Rad (Hercules, CA) according to our previously described methods [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

Andersen,

Milefchik,

Papworth

et al. 2024

Epigenetics

Self Cite

View full text Add to dashboard Cite

Currently, clinicians use their judgement and indices such as the Prediction of Alcohol Withdrawal Syndrome Scale (PAWSS) to determine whether patients are admitted to hospitals for consideration of withdrawal syndrome (AWS). However, only a fraction of those admitted will experience severe AWS. Previously, we and others have shown that epigenetic indices, such as the Alcohol T-Score (ATS), can quantify recent alcohol consumption. However, whether these or other alcohol biomarkers, such as carbohydrate deficient transferrin (CDT), could identify those at risk for severe AWS is unknown. To determine this, we first conducted genome-wide DNA methylation analyses of subjects entering and exiting alcohol treatment to identify loci whose methylation quickly reverted as a function of abstinence. We then tested whether methylation at a rapidly reverting locus, cg07375256, or other existing metrics including PAWSS scores, CDT levels, or ATS, could predict outcome in 125 subjects admitted for consideration of AWS. We found that PAWSS did not significantly predict severe AWS nor seizures. However, methylation at cg07375256 ( ZSCAN25 ) and CDT strongly predicted severe AWS with ATS ( p < 0.007) and cg07375256 ( p < 6 × 10–5) methylation also predicting AWS associated seizures. We conclude that epigenetic methods can predict those likely to experience severe AWS and that the use of these or similar Precision Epigenetic approaches could better guide AWS management.

show abstract

Epigenetic biomarkers for smoking cessation

Cited by 8 publications

References 96 publications

Validation of an Integrated Genetic‐Epigenetic Test for the Assessment of Coronary Heart Disease

Validation of an Integrated Genetic‐Epigenetic Test for the Assessment of Coronary Heart Disease

The Reversion of the Epigenetic Signature of Coronary Heart Disease in Response to Smoking Cessation

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

Contact Info

Product

Resources

About