A Four Marker Digital PCR Toolkit for Detecting Heavy Alcohol Consumption and the Effectiveness of Its Treatment

Abstract

Background.—Heavy alcohol consumption (HAC) is a shared concern of the forensic, medical and insurance underwriting communities. Unfortunately, there is a relative lack of clinically employable tools for detecting HAC and monitoring treatment response. Building on the results of 3 genome wide methylation studies, we have previously shown in a small group of samples that methylation sensitive digital PCR assays (MSdPCR) have the potential to accurately classify individuals with respect to HAC in a small set of individuals. Objective.—We now expand on those earlier findings using data and biomaterials from 143 participants with current HAC and 200 abstinent controls. Results.—We show that a set of 4 digital PCR assays that have a receiver operating characteristic (ROC) area under the curve (AUC) of 0.96 for detecting those with HAC. After a mean of 21 days of inpatient enforced abstinence, methylation status at one of these markers, cg04987734, began to revert to baseline values. Re-examination of methylation data from our smaller 2014 study with respect to this locus demonstrated a similarly significant reversion pattern at cg04987734 in association with treatment enforced abstinence. Conclusions.—We conclude that clinically implementable dPCR tools can sensitively detect the presence of HAC and that they show promise for monitoring alcohol treatment results. These dPCR tools could be useful to clinicians and researchers in monitoring those enrolled in substance use disorder treatment, employee wellness programs and insurance underwriting.

The relationship of smoking to cg05575921 methylation in blood and saliva DNA samples from several studies

“…The Alcohol Cessation (ALC2A) subjects were collected for a project whose goal was to develop a blood-based test for heavy alcohol consumption 27 . In this protocol, two distinct groups of subjects were collected.…”

Array-Based Epigenetic Aging Indices May Be Racially Biased

“…If the amount of confounding is proportional to the number of probes, then the effects on this index are likely less severe. In addition, many of the CpG sites in their index, such as cg04987734 and cg05575921, load specifically on smoking and drinking consumption and have no known ethnic bias in their set points [ 48 , 49 ]. In contrast, the GrimAge index, which also has considerable heritability, uses information from over 1000 CpG probes [ 26 ].…”

A Comparison of the Predictive Power of DNA Methylation with Carbohydrate Deficient Transferrin for Heavy Alcohol Consumption

“…sera) and clinical data included in these analyses were taken from a previously described case and control analysis of HAC whose conduct was approved by the Western Institutional Review Board (www.wirb. com) [20].…”

“…In a recent study, we test the ability of the Alcohol Signature dPCR panel to predict HAC status in a cohort of 212 self-reported abstinent controls and 143 subjects admitted for alcohol treatment [20]. Overall, the Alcohol Signature dPCR panel predicted HAC status with an AUC of 0.95 with no effects of gender or ethnicity detected.…”