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Genome-wide association study of comorbid depressive syndrome and alcohol dependence
Journal article   Peer reviewed

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, …
Psychiatric genetics, Vol.22(1), pp.31-41
02/2012
DOI: 10.1097/YPG.0b013e32834acd07
PMCID: PMC3241912
PMID: 22064162
url
https://scholarworks.indianapolis.iu.edu/bitstreams/1014ed42-166e-4da7-9590-16a4ed585ac5/downloadView
Open Access

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.
 Comorbidity genetics of alcoholism genetic risk depressive syndrome

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