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 Nurnberger, Marc A. Schuckit, Bernice Porjesz, Danielle M. Dick

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)31-41
Number of pages11
JournalPsychiatric Genetics
Volume22
Issue number1
DOIs
StatePublished - Feb 2012

Fingerprint

Genome-Wide Association Study
Depressive Disorder
Alcoholism
Phenotype
Single Nucleotide Polymorphism
Depression
Diagnostic and Statistical Manual of Mental Disorders
Genes
Psychiatry
Gene Ontology
Twin Studies
Genome
Brain

Keywords

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

ASJC Scopus subject areas

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

Cite this

Edwards, A. C., Aliev, F., Bierut, L. J., Bucholz, K. K., Edenberg, H., Hesselbrock, V., ... Dick, D. M. (2012). Genome-wide association study of comorbid depressive syndrome and alcohol dependence. Psychiatric Genetics, 22(1), 31-41. https://doi.org/10.1097/YPG.0b013e32834acd07

Genome-wide association study of comorbid depressive syndrome and alcohol dependence. / Edwards, Alexis C.; Aliev, Fazil; Bierut, Laura J.; Bucholz, Kathleen K.; Edenberg, Howard; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Nurnberger, John; Schuckit, Marc A.; Porjesz, Bernice; Dick, Danielle M.

In: Psychiatric Genetics, Vol. 22, No. 1, 02.2012, p. 31-41.

Research output: Contribution to journalArticle

Edwards, AC, Aliev, F, Bierut, LJ, Bucholz, KK, Edenberg, H, Hesselbrock, V, Kramer, J, Kuperman, S, Nurnberger, J, Schuckit, MA, Porjesz, B & Dick, DM 2012, 'Genome-wide association study of comorbid depressive syndrome and alcohol dependence', Psychiatric Genetics, vol. 22, no. 1, pp. 31-41. https://doi.org/10.1097/YPG.0b013e32834acd07
Edwards, Alexis C. ; Aliev, Fazil ; Bierut, Laura J. ; Bucholz, Kathleen K. ; Edenberg, Howard ; Hesselbrock, Victor ; Kramer, John ; Kuperman, Samuel ; Nurnberger, John ; Schuckit, Marc A. ; Porjesz, Bernice ; Dick, Danielle M. / Genome-wide association study of comorbid depressive syndrome and alcohol dependence. In: Psychiatric Genetics. 2012 ; Vol. 22, No. 1. pp. 31-41.
@article{252d1715252640e583f548fe30c28b59,
title = "Genome-wide association study of comorbid depressive syndrome and alcohol dependence",
abstract = "Lippincott Williams & Wilkins.",
keywords = "comorbidity, depressive syndrome, genetic risk, genetics of alcoholism",
author = "Edwards, {Alexis C.} and Fazil Aliev and Bierut, {Laura J.} and Bucholz, {Kathleen K.} and Howard Edenberg and Victor Hesselbrock and John Kramer and Samuel Kuperman and John Nurnberger and Schuckit, {Marc A.} and Bernice Porjesz and Dick, {Danielle M.}",
year = "2012",
month = "2",
doi = "10.1097/YPG.0b013e32834acd07",
language = "English",
volume = "22",
pages = "31--41",
journal = "Psychiatric Genetics",
issn = "0955-8829",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Genome-wide association study of comorbid depressive syndrome and alcohol dependence

AU - Edwards, Alexis C.

AU - Aliev, Fazil

AU - Bierut, Laura J.

AU - Bucholz, Kathleen K.

AU - Edenberg, Howard

AU - Hesselbrock, Victor

AU - Kramer, John

AU - Kuperman, Samuel

AU - Nurnberger, John

AU - Schuckit, Marc A.

AU - Porjesz, Bernice

AU - Dick, Danielle M.

PY - 2012/2

Y1 - 2012/2

N2 - Lippincott Williams & Wilkins.

AB - Lippincott Williams & Wilkins.

KW - comorbidity

KW - depressive syndrome

KW - genetic risk

KW - genetics of alcoholism

UR - http://www.scopus.com/inward/record.url?scp=84655162267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84655162267&partnerID=8YFLogxK

U2 - 10.1097/YPG.0b013e32834acd07

DO - 10.1097/YPG.0b013e32834acd07

M3 - Article

VL - 22

SP - 31

EP - 41

JO - Psychiatric Genetics

JF - Psychiatric Genetics

SN - 0955-8829

IS - 1

ER -