title: Review: DNA methylation and alcohol use disorders: Progress and challenges.
abstract: OBJECTIVE
  Risk for alcohol use disorders (AUDs) is influenced by gene-environment interactions. Environmental factors can affect gene expression through epigenetic mechanisms such as DNA methylation. This review outlines the findings regarding the association of DNA methylation and AUDs.
  
  
  METHODS
  We searched PubMed (by April 2016) and identified 29 studies that examined the association of DNA methylation and AUDs. We also evaluated the methods used in these studies.
  
  
  RESULTS
  Two studies demonstrated elevated global (repetitive element) DNA methylation levels in AUD subjects. Fifteen candidate gene studies showed hypermethylation of promoter regions of six genes (AVP, DNMT3B, HERP, HTR3A, OPRM1, and SNCA) or hypomethylation of the GDAP1 promoter region in AUD subjects. Five genome-wide DNA methylation studies demonstrated widespread DNA methylation changes across the genome in AUD subjects. Six studies showed significant correlations of DNA methylation with gene expression in AUD subjects. Three studies revealed interactive effects of genetic variation and DNA methylation on susceptibility to AUDs. Most studies analyzed AUD-associated DNA methylation changes in the peripheral blood; a few studies examined DNA methylation changes in postmortem brains of AUD subjects.
  
  
  CONCLUSIONS
  Chronic alcohol consumption may result in DNA methylation changes, leading to neuroadaptations that may underlie some of the mechanisms of AUD risk and persistence. Future studies are needed to confirm the few existing results, and then to elucidate whether DNA methylation changes are the cause or consequence of AUDs.
  
  
  CONCLUSIONS
  DNA methylation profiles may be used to assess AUD status or monitor AUD treatment response. (Am J Addict 2017;26:502-515).
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.|VA Connecticut Healthcare System, West Haven, Connecticut.|Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.|Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*