title: Genome-wide association study of comorbid depressive syndrome and alcohol dependence.
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.
  
  
  CONCLUSIONS
  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.
authors: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia 23298-0126, USA. aedwards5@vcu.edu
authors: Alexis C
authors: AC
authors: Edwards
authors: Fazil
authors: F
authors: Aliev
authors: Laura J
authors: LJ
authors: Bierut
authors: Kathleen K
authors: KK
authors: Bucholz
authors: Howard
authors: H
authors: Edenberg
authors: Victor
authors: V
authors: Hesselbrock
authors: John
authors: J
authors: Kramer
authors: Samuel
authors: S
authors: Kuperman
authors: John I
authors: JI
authors: Nurnberger
authors: Marc A
authors: MA
authors: Schuckit
authors: Bernice
authors: B
authors: Porjesz
authors: Danielle M
authors: DM
authors: Dick
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D015897:Comorbidity; D003866:Depressive Disorder / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: D005819:Genetic Markers