Epigenetic and Proteomic Biomarkers of Elevated Alcohol Use Predict Epigenetic Aging and Cell-Type variation Better Than Self-Report

Abstract

Excessive alcohol consumption (EAC) has a generally accepted effect on morbidity and mortality, outcomes thought to be reflected in measures of epigenetic aging (EA). As the association of self-reported EAC with EA has not been consistent with these expectations, underscoring the need for readily employable non-self-report tools for accurately assessing and monitoring the contribution of EAC to accelerated EA, newly developed alcohol consumption DNA methylation indices, such as the Alcohol T Score (ATS) and Methyl DetectR (MDR), may be helpful. To test that hypothesis, we used these new indices along with the carbohydrate deficient transferrin (CDT), concurrent as well as past self-reports of EAC, and well-established measures of cigarette smoking to examine the relationship of EAC to both accelerated EA and immune cell counts in a cohort of 437 young Black American adults. We found that MDR, CDT, and ATS were intercorrelated, even after controlling for gender and cotinine effects. Correlations between EA and self-reported EAC were low or non-significant, replicating prior research, whereas correlations with non-self-report indices were significant and more substantial. Comparing non-self-report indices showed that the ATS predicted more than four times as much variance in EA, CDT4 cells and B-cells as for both the MDR and CDT, and better predicted indices of accelerated EA. We conclude that each of the non-self-report indices have differing predictive capacities with respect to key alcohol-related health outcomes, and that the ATS may be particularly useful for clinicians seeking to understand and prevent accelerated EA. The results also underscore the likelihood of substantial underestimates of problematic use when self-report is used and a reduction in correlations with EA and variance in cell-types.

Do Loneliness and Per Capita Income Combine to Increase the Pace of Biological Aging for Black Adults across Late Middle Age?

“…Measurement issues have often made direct assessment of health impacts, health behaviors, and pro-inflammatory processes difficult, and have forced researchers to rely on self-reported health and behavior. Recently, there have been developments in the use of methylation markers that allow more direct assessment in each of these domains, allowing researchers to bypass self-report [ 22 , 23 ]. In addition, epigenetic measurement has the potential to help examine mechanisms of effect.…”

ZSCAN25 methylation predicts seizures and severe alcohol withdrawal syndrome

“…Indeed, in our clinical experience (BP, AA, and RP), we have found that patients often misrepresent their alcohol use history. Although others may disagree, in our research experience, we standardly employ multiple biomarkers of alcohol consumption including the CDT and epigenetic biomarkers to assess alcohol use in our subjects and routinely find much stronger relationships between biomarkers of alcohol use to one another and to key outcomes than to those found with self-report [ 10 , 12 , 45 ]. When considering the circumstances in which most of the subjects in this study were presented, this is certainly understandable.…”

“…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 ].…”

“…Specifically, in prior work, we have shown that a metric composed of the unweighted Z-scores of the results from four methylation sensitive digital PCR assays (MSdPCR), referred to as the Alcohol T Score (ATS), is strongly correlated with other objective biomarkers of heavy alcohol consumption (HAC) and accurately predicted those who were admitted for residential treatment of AUD [ 9 , 10 ]. However, whereas this tool may be useful for predicting both chronic HAC and the biological consequences of HAC [ 11 , 12 ], the dynamic response time of the four loci is slow, with a half-time of reversion of the most responsive locus, cg04987734, being on the order of 3 months [ 9 ]. Whereas this slow dynamic may make the ATS useful for detecting chronic HAC, it may make the ATS less useful for other purposes.…”