Psychiatric Genetics

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Psychiatric Genetics:
doi: 10.1097/YPG.0b013e32834acd07
Original Articles

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

Edwards, Alexis C.a; Aliev, Fazila,h; Bierut, Laura J.b; Bucholz, Kathleen K.b; Edenberg, Howardc; Hesselbrock, Victord; Kramer, Johne; Kuperman, Samuele; Nurnberger, John I. Jrc; Schuckit, Marc A.f; Porjesz, Berniceg; Dick, Danielle M.a

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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 1×10−3 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.

© 2012 Lippincott Williams & Wilkins, Inc.

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