Genome-wide association study of comorbid depressive syndrome and alcohol dependence

Psychiatr Genet. 2012 Feb;22(1):31-41. doi: 10.1097/YPG.0b013e32834acd07.

Abstract

Objective: Depression and alcohol dependence (AD) are common psychiatric disorders that often co-occur. Both disorders are genetically influenced, with heritability estimates in the range of 35-60%. In addition, evidence from twin studies suggests that AD and depression are genetically correlated. Herein, we report results from a genome-wide association study of a comorbid phenotype, in which cases meet the Diagnostic and Statistical Manual of Mental Disorders-IV symptom threshold for major depressive symptomatology and the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for AD.

Methods: Samples (N=467 cases and N=407 controls) were of European-American descent and were genotyped using the Illumina Human 1M BeadChip array.

Results: Although no single-nucleotide polymorphism (SNP) meets genome-wide significance criteria, we identified 10 markers with P values less than 1 × 10(-5), seven of which are located in known genes, which have not been previously implicated in either disorder. Genes harboring SNPs yielding P values less than 1 × 10(-5) are functionally enriched for a number of gene ontology categories, notably several related to glutamatergic function. Investigation of expression localization using online resources suggests that these genes are expressed across a variety of tissues, including behaviorally relevant brain regions. Genes that have been previously associated with depression, AD, or other addiction-related phenotypes - such as CDH13, CSMD2, GRID1, and HTR1B - were implicated by nominally significant SNPs. Finally, the degree of overlap of significant SNPs between a comorbid phenotype and an AD-only phenotype is modest.

Conclusion: These results underscore the complex genomic influences on psychiatric phenotypes and suggest that a comorbid phenotype is partially influenced by genetic variants that do not affect AD alone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alcoholism / complications
  • Alcoholism / epidemiology*
  • Alcoholism / genetics*
  • Case-Control Studies
  • Comorbidity
  • Depressive Disorder / complications
  • Depressive Disorder / epidemiology*
  • Depressive Disorder / genetics*
  • Female
  • Gene Expression Regulation
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • United States / epidemiology

Substances

  • Genetic Markers