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, 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

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)988-996
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume34
Issue number6
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Corticotropin-Releasing Hormone Receptors
Polymorphism
Evoked Potentials
Alcoholism
Single Nucleotide Polymorphism
Nucleotides
Genes
Alcohols
Endophenotypes
P300 Event-Related Potentials
Psychiatry
Electrophysiology
Self Administration
Automatic Data Processing
Animals
Ethanol
Animal Models
Processing

Keywords

  • Corticotropin Releasing Factor (CRF)
  • Disinhibition
  • Endophenotype
  • P3
  • Stress

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology
  • Medicine(all)

Cite this

Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. / Chen, Andrew C H; Manz, Niklas; Tang, Yongqiang; Rangaswamy, Madhavi; Almasy, Laura; Kuperman, Samuel; Nurnberger, John; O'Connor, Sean J.; Edenberg, Howard J.; Schuckit, Marc A.; Tischfield, Jay; Foroud, Tatiana; Bierut, Laura J.; Rohrbaugh, John; Rice, John P.; Goate, Alison; Hesselbrock, Victor; Porjesz, Bernice.

In: Alcoholism: Clinical and Experimental Research, Vol. 34, No. 6, 2010, p. 988-996.

Research output: Contribution to journalArticle

Chen, ACH, Manz, N, Tang, Y, Rangaswamy, M, Almasy, L, Kuperman, S, Nurnberger, J, O'Connor, SJ, Edenberg, HJ, Schuckit, MA, Tischfield, J, Foroud, T, Bierut, LJ, Rohrbaugh, J, Rice, JP, Goate, A, Hesselbrock, V & Porjesz, B 2010, 'Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence', Alcoholism: Clinical and Experimental Research, vol. 34, no. 6, pp. 988-996. https://doi.org/10.1111/j.1530-0277.2010.01173.x
Chen, Andrew C H ; Manz, Niklas ; Tang, Yongqiang ; Rangaswamy, Madhavi ; Almasy, Laura ; Kuperman, Samuel ; Nurnberger, John ; O'Connor, Sean J. ; Edenberg, Howard J. ; Schuckit, Marc A. ; Tischfield, Jay ; Foroud, Tatiana ; Bierut, Laura J. ; Rohrbaugh, John ; Rice, John P. ; Goate, Alison ; Hesselbrock, Victor ; Porjesz, Bernice. / Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. In: Alcoholism: Clinical and Experimental Research. 2010 ; Vol. 34, No. 6. pp. 988-996.
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T1 - Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence

AU - Chen, Andrew C H

AU - Manz, Niklas

AU - Tang, Yongqiang

AU - Rangaswamy, Madhavi

AU - Almasy, Laura

AU - Kuperman, Samuel

AU - Nurnberger, John

AU - O'Connor, Sean J.

AU - Edenberg, Howard J.

AU - Schuckit, Marc A.

AU - Tischfield, Jay

AU - Foroud, Tatiana

AU - Bierut, Laura J.

AU - Rohrbaugh, John

AU - Rice, John P.

AU - Goate, Alison

AU - Hesselbrock, Victor

AU - Porjesz, Bernice

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N2 - Background: 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. Methods: 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. Results: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Conclusions: 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.

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