Journal article
Genome-wide and digital polymerase chain reaction epigenetic assessments of alcohol consumption
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.177(5), pp.479-488
07/2018
DOI: 10.1002/ajmg.b.32636
PMID: 29704316
Abstract
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.
Details
- Title: Subtitle
- Genome-wide and digital polymerase chain reaction epigenetic assessments of alcohol consumption
- Creators
- Robert Philibert - Department of Psychiatry, University of Iowa, Iowa City, IowaMeesha Dogan - Cardio Diagnostics, Coralville, IowaAmanda Noel - Behavioral Diagnostics, Coralville, IowaShelly Miller - Behavioral Diagnostics, Coralville, IowaBrianna Krukow - Behavioral Diagnostics, Coralville, IowaEmma Papworth - Behavioral Diagnostics, Coralville, IowaJoseph Cowley - Center for Alcohol and Drug Services, Davenport, IowaApril Knudsen - Prelude Behavioral Services, Des Moines, IowaSteven R H Beach - University of Georgia, Athens, GeorgiaDonald Black - Department of Psychiatry, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.177(5), pp.479-488
- DOI
- 10.1002/ajmg.b.32636
- PMID
- 29704316
- NLM abbreviation
- Am J Med Genet B Neuropsychiatr Genet
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Publisher
- United States
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R44AA022041, R01DA037648, R44 CA213507
- Language
- English
- Date published
- 07/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003444702771
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