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

Abstract

Currently, the most commonly used biomarker of alcohol consumption patterns is carbohydratedeficient transferrin (CDT). However, the CDT has limited sensitivity and requires the use of blood. Recently, we have shown that digital DNA methylation techniques can both sensitively and specifically detect heavy alcohol consumption (HAC) using DNA from blood or saliva. In order to better understand the relative performance characteristics of these two tests, we compared an Alcohol T-Score (ATS) derived from our prior study and serum CDT levels in 313 (182 controls and 131 HAC cases) subjects discordant for HAC. Overall, the Receiver Operating Characteristic (ROC) area under the curve (AUC) analyses showed that DNA methylation predicted HAC status better than CDT with AUCs of 0.96 and 0.87, respectively (p < 0.0001). The performance of the CDT was affected by gender while the ATS was not, while both were affected by age. We conclude that DNA methylation is a promising method for quantifying HAC and that further studies to better refine its strengths and limitations are in order.

A simple, rapid, interpretable, actionable and implementable digital PCR based mortality index

“…Furthermore, if the patient/subject has recently quit smoking, he/she should be periodically monitored to ensure that relapse does not occur. Similarly, although cg04987734 and cg02583484 are not as sensitive and specific for heavy alcohol consumption (HAC) as cg05575921 is for smoking, the individual AUC at these loci using the dPCR assay are still high enough (~0.85 each) to suggest that we believe that anyone with significant elevation of cg04987734 or cg02583484 methylation should be evaluated for an alcohol use disorder either through the use of the full dPCR methylation panel, which has an AUC of 0.95 for HAC and outperforms conventional carbohydratedeficient transferrin testing [50], or through referral to a mental health professional [51]. Finally, significant changes in cg00300879 or cg19693031, particularly in the presence of significant cg05575921 demethylation, may suggest the need for further cardiovascular or HbA1c testing.…”

Alcohol Use Intensity Decreases in Response to Successful Smoking Cessation Therapy

“…The DNA was prepared from whole blood using cold protein precipitation as previously described [ 15 , 20 , 21 , 23 , 24 ]. Serum cotinine levels were determined by the University of Iowa Diagnostic Laboratories under standard clinical processes.…”

“…However, the current generation of alcohol biomarkers is poorly suited for use in most research studies. The gold standard for assessing alcohol consumption in clinical trials is carbohydrate-deficient transferrin (CDT) [ 14 , 15 , 16 ]. However, this test is known to have limited sensitivity and requires venipuncture to obtain serum.…”

“…The use of DNA methylation to assess alcohol consumption status may be a better alternative for clinical studies of cigarette and alcohol use. Recently, in a blinded study conducted with a well-known insurance testing laboratory, we showed that a metric referred to as Alcohol T-Score (ATS) is more accurate than the CDT in predicting HAC [ 15 , 17 ]. What is more, different from CDT and PEth testing, the ATS can be assessed using DNA prepared from either blood or saliva [ 18 ].…”

Epigenetic Analyses of Alcohol Consumption in Combustible and Non-Combustible Nicotine Product Users

“…We devised an Alcohol T Score metric calculated from the methylation values of four loci, cg02583484, cg04987734, cg09935388, and cg04583842 [ 39 ]. We have demonstrated that the ATS outperforms the CDT with an AUC of 0.96 for detecting those with heavy alcohol consumption [ 46 ]. Similar to cg05575921, one of the alcohol-sensitive loci demonstrated reversion to baseline methylation levels with treatment enforced alcohol abstinence [ 39 ].…”