Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence

Andrew C H Chen; Niklas Manz; Yongqiang Tang; Madhavi Rangaswamy; Laura Almasy; Samuel Kuperman; John  Nurnberger Jr; Sean J O'Connor; Howard J Edenberg; Marc A Schuckit; Jay Tischfield; Tatiana Foroud; Laura J Bierut; John Rohrbaugh; John P Rice; Alison Goate; Victor Hesselbrock; Bernice Porjesz

doi:10.1111/j.1530-0277.2010.01173.x

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Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence

Journal article

Peer reviewed

Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence

Andrew C H Chen, Niklas Manz, Yongqiang Tang, Madhavi Rangaswamy, Laura Almasy, Samuel Kuperman, John Nurnberger Jr, Sean J O'Connor, Howard J Edenberg, Marc A Schuckit, …

Alcoholism, clinical and experimental research, Vol.34(6), pp.988-996

06/2010

DOI: 10.1111/j.1530-0277.2010.01173.x

PMCID: PMC3248053

PMID: 20374216

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Abstract

Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

Phenotype

European Continental Ancestry Group - genetics

Event-Related Potentials, P300 - physiology

Humans

Linkage Disequilibrium - genetics

Receptors, Corticotropin-Releasing Hormone - genetics

Genotype

Male

Case-Control Studies

Young Adult

Receptors, Corticotropin-Releasing Hormone - physiology

Event-Related Potentials, P300 - genetics

Adolescent

Polymorphism, Single Nucleotide - genetics

Adult

Alcoholism - genetics

Female

Aged

Electrophysiological Phenomena

Alcoholism - physiopathology

Quantitative Trait Loci - genetics

Details

Title: Subtitle: Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence
Creators: Andrew C H Chen - Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
Niklas Manz
Yongqiang Tang
Madhavi Rangaswamy
Laura Almasy
Samuel Kuperman
John Nurnberger Jr
Sean J O'Connor
Howard J Edenberg
Marc A Schuckit
Jay Tischfield
Tatiana Foroud
Laura J Bierut
John Rohrbaugh
John P Rice
Alison Goate
Victor Hesselbrock
Bernice Porjesz
Resource Type: Journal article
Publication Details: Alcoholism, clinical and experimental research, Vol.34(6), pp.988-996
DOI: 10.1111/j.1530-0277.2010.01173.x
PMID: 20374216
PMCID: PMC3248053
NLM abbreviation: Alcohol Clin Exp Res
ISSN: 0145-6008
eISSN: 1530-0277
Publisher: Wiley; England
Grant note: U10 AA008401-23 / NIAAA NIH HHS U10AA008401 / NIAAA NIH HHS U10 AA008401 / NIAAA NIH HHS
Language: English
Date published: 06/2010
Academic Unit: Psychiatry; Stead Family Department of Pediatrics
Record Identifier: 9984003459402771

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