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Methylation Biomarker of Chronic Heavy Alcohol Consumption (HAC), but Not Acute HAC, Predicts All-Cause Mortality in
Steven R H Beach1, James A Mills2, Jeffrey D Long2,3
1Department of Psychology, University of Georgia, Athens, GA 30602, USA.
Insights
Chronic heavy alcohol consumption (HAC), measured by the alcohol T-score (ATS), strongly predicts mortality, unlike short-term drinking. This highlights limitations in self-reported alcohol use and the value of biomarkers for assessing HAC.
Area of Science:
- Biomarkers and Epigenetics
- Public Health and Epidemiology
- Toxicology and Environmental Health
Background:
- Quantifying heavy alcohol consumption's mortality impact is challenging due to consumption variability and self-report inaccuracies.
- Previous research established DNA methylation biomarker alcohol T-score (ATS) for chronic heavy alcohol consumption (HAC) as a strong mortality predictor.
- The impact of short-term heavy alcohol use (binge drinking) on mortality, using biomarkers, remained unexamined.
Purpose of the Study:
- To evaluate the predictive power of chronic HAC (ATS), smoking (cg05575921), and short-term HAC (cg07375256) biomarkers on all-cause mortality.
- To compare the performance of different biomarker combinations in predicting mortality.
- To assess the relationship between biomarkers and self-reported alcohol use, and identify potential biases in self-reporting.
Main Methods:
- Utilized Cox Proportional Hazards Regression Modeling in 708 participants from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
- Assessed DNA methylation biomarkers for smoking (cg05575921), chronic HAC (ATS), and short-term HAC (cg07375256).
- Employed Akaike's Information Criterion for model comparison and conducted sensitivity analyses.
Main Results:
- The ATS was the strongest single predictor of mortality among tested variables, outperforming short-term HAC biomarkers.
- A model including age, sex, smoking biomarker (cg05575921), and ATS demonstrated the best mortality prediction.
- Short-term HAC biomarker (cg07375256) did not improve mortality prediction and showed weak associations with self-reported alcohol use.
Conclusions:
- Chronic HAC, assessed via ATS, significantly impacts mortality, whereas short-term HAC does not.
- The study underscores the limitations of self-reported alcohol use for predicting mortality.
- Biomarker assessment of chronic HAC is valuable, particularly when combined with smoking status evaluation.
Background:
Due to variability in patterns of consumption as well as well-known difficulties in obtaining valid self-report from heavy drinkers, quantifying the effects of heavy alcohol consumption on mortality is challenging. Using a DNA methylation biomarker of chronic heavy alcohol consumption (HAC) named the alcohol T-score (ATS), we previously showed that chronic HAC was a strong predictor of mortality. However, whether there is a similar effect when measures of shorter-term heavy alcohol use, i.e., recent "binge" drinking, were used to predict mortality was not examined. This is a critical issue because most biomarkers of HAC assess only short-term HAC.
Methods:
Therefore, we examined the prediction of all-cause mortality from a DNA methylation biomarker of smoking (cg05575921), the ATS and a short-term biomarker of recent heavy alcohol use (cg07375256) in 708 subjects from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial using Cox Proportional Hazards Regression Modeling. Models were compared using Akaike's Information Criterion.
Results:
The ATS was the best single predictor among three-variable models that included controls for sex and age. Of the possible four variable models, the model consisting of age, sex, cg05575921 methylation and ATS best predicted mortality. The addition of cg07375256 methylation did not improve model performance. In sensitivity analyses using only participants who provided alcohol SR (n = 639), the importance of the ATS and cg05575921 was replicated. We also found that ATS values were higher among those who declined to provide self-report alcohol use, indicating that missing self-report data about alcohol intake are not missing at random, and sometimes reflects elevated alcohol consumption. Finally, cg05575921 methylation was strongly associated with ATS values but only weakly with alcohol SR and not at all with cg07375256 methylation.
Conclusions:
Accordingly, this study indicates a strong effect of chronic HAC, but not short-term HAC, on mortality, further highlights the limitations of self-reported alcohol use in the prediction of all-cause mortality and indicates the value of assessing HAC in addition to smoking.
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