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

Alexis C. Edwards, Fazil Aliev, Laura J. Bierut, Kathleen K. Bucholz, Howard Edenberg, Victor Hesselbrock, John Kramer, Samuel Kuperman, John I. Nurnberger, Marc A. Schuckit, Bernice Porjesz, Danielle M. Dick

Research output: Contribution to journalArticle

69 Scopus citations


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 -3 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.

Original languageEnglish (US)
Pages (from-to)31-41
Number of pages11
JournalPsychiatric genetics
Issue number1
StatePublished - Feb 1 2012


  • comorbidity
  • depressive syndrome
  • genetic risk
  • genetics of alcoholism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Genetics
  • Biological Psychiatry

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  • Cite this

    Edwards, A. C., Aliev, F., Bierut, L. J., Bucholz, K. K., Edenberg, H., Hesselbrock, V., Kramer, J., Kuperman, S., Nurnberger, J. I., Schuckit, M. A., Porjesz, B., & Dick, D. M. (2012). Genome-wide association study of comorbid depressive syndrome and alcohol dependence. Psychiatric genetics, 22(1), 31-41.