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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
Author(s) -
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
Publication year - 2010
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2010.01173.x
Subject(s) - endophenotype , single nucleotide polymorphism , alcohol dependence , transmission disequilibrium test , psychology , alcohol use disorder , genetic association , trait , genetics , gene , biology , psychiatry , alcohol , genotype , biochemistry , cognition , computer science , programming language
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.