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A Rat Methyl-Seq Platform to Identify Epigenetic Changes Associated with Stress Exposure
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Array-based profiling of DNA methylation changes associated with alcohol dependence.

Huiping Zhang1, Aryeh I Herman, Henry R Kranzler

  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516, USA. huiping.zhang@yale.edu

Alcoholism, Clinical and Experimental Research
|August 29, 2012
PubMed
Summary
This summary is machine-generated.

DNA methylation patterns are linked to alcohol dependence (AD) risk differently across populations. Epigenetic modifications and genetic factors likely interact to influence AD vulnerability.

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Area of Science:

  • Epigenetics
  • Neuroscience
  • Genetics

Background:

  • DNA methylation is a key epigenetic mechanism potentially influencing vulnerability to various disorders.
  • Alcohol dependence (AD) is a complex disorder where epigenetic factors may play a role.

Purpose of the Study:

  • To investigate DNA methylation differences in peripheral blood between individuals with and without alcohol dependence.
  • To examine population-specific epigenetic alterations associated with alcohol dependence in African Americans and European Americans.

Main Methods:

  • Analyzed DNA methylation levels of 384 CpGs in 82 candidate genes in African American and European American cohorts using Illumina GoldenGate Methylation Array.
  • Utilized multivariate analyses of covariance to assess the association between AD and DNA methylation, controlling for covariates.
  • Replicated findings in a separate European American sample using Sequenom's MassARRAY EpiTYPER technology.

Main Results:

  • Identified hypermethylation in 2 CpGs (GABRB3, POMC) in African American AD cases compared to controls.
  • Found hypermethylation in 6 CpGs across 6 genes (HTR3A, NCAM1, DRD4, MBD3, HTR2B, GRIN1) in European American AD cases.
  • Observed a trend of higher methylation at CpG cg08989585 in the HTR3A promoter in European American AD cases in the replication sample, though not statistically significant.

Conclusions:

  • DNA methylation profiles associated with alcohol dependence exhibit population-specific patterns.
  • The predisposition to alcohol dependence may arise from a complex interaction between genetic variations and epigenetic modifications.