Genome wide and Digital PCR Epigenetic Assessments of Alcohol Consumption

Philibert, Robert; Dogan, Meeshanthini; Noel, Amanda; Miller, Shelly;  Krukow, Brianna; Cowley, Joseph; Knudsen, April; Beach, Steven; Black, Donald W.  Genome wide and Digital PCR Epigenetic Assessments of Alcohol Consumption. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

Link: In Press


The lack of readily employable biomarkers of alcohol consumption is a barrier to both clinicians and researchers. In 2014, we published a preliminary DNA methylation signature of heavy alcohol consumption that remits as a function of abstinence. Herein, we present new genome wide methylation findings from a cohort of additional subjects and a meta-analysis of the data. Using DNA from 47 consecutive heavy drinkers and 47 abstinent controls, we replicate the 2014 results and show that 21,221 CpG residues are differentially methylated in heavy drinkers. Meta-analysis of all data from the 448,058 probes common to the two methylation platforms show a similarly profound signature with confirmation of findings from other groups. Principal components analyses show that genome wide methylation changes in response to alcohol consumption load on two major factors with one component accounting at least 50% of the total variance in both smokers and non-smoking alcoholics. Using data from the arrays, we derive a panel of 5 methylation probes that classifies use status with a Receiver Operator Characteristic Area Under the curve (AUC) of 0.97. Finally, using droplet digital PCR, we convert these array based findings to two marker assay with an AUC of 0.95 and a four marker set AUC of 0.98. We conclude that DNA methylation assessments are capable of quantifying alcohol use status and suggest that that readily employable digital PCR approaches for substance consumption may find widespread use in alcohol related research and patient care.