Premium
Genome‐wide and digital polymerase chain reaction epigenetic assessments of alcohol consumption
Author(s) -
Philibert Robert,
Dogan Meesha,
Noel Amanda,
Miller Shelly,
Krukow Brianna,
Papworth Emma,
Cowley Joseph,
Knudsen April,
Beach Steven R. H.,
Black Donald
Publication year - 2018
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32636
Subject(s) - digital polymerase chain reaction , dna methylation , context (archaeology) , methylation , epigenetics , abstinence , alcohol , polymerase chain reaction , computational biology , alcohol dependence , cpg site , biology , medicine , genetics , gene , biochemistry , gene expression , psychiatry , paleontology
The lack of readily employable biomarkers of alcohol consumption is a problem for 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 admitted for alcohol detoxification in the context of alcohol treatment and 47 abstinent controls, we replicate the 2014 results and show that 21,221 CpG residues are differentially methylated in active heavy drinkers. Meta‐analysis of all data from the 448,058 probes common to the two methylation platforms shows 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 nonsmoking alcoholics. Using data from the arrays, we derive a panel of five methylation probes that classifies use status with a receiver operator characteristic area under the curve (AUC) of 0.97. Finally, using droplet digital polymerase chain reaction (PCR), we convert these array‐based findings to two marker assays 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 readily employable digital PCR approaches for substance consumption may find widespread use in alcohol‐related research and patient care.