title: Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.
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.
authors.affiliation: Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Andrew C H
authors.initials: AC
authors.lastname: Chen
authors.forename: Niklas
authors.initials: N
authors.lastname: Manz
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Tang
authors.forename: Madhavi
authors.initials: M
authors.lastname: Rangaswamy
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Samuel
authors.initials: S
authors.lastname: Kuperman
authors.forename: John
authors.initials: J
authors.lastname: Nurnberger
authors.forename: Sean J
authors.initials: SJ
authors.lastname: O'Connor
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: John
authors.initials: J
authors.lastname: Rohrbaugh
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D055724:Electrophysiological Phenomena; D018913:Event-Related Potentials, P300 / Q000235:genetics* / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000502:physiology; D044465:White People / Q000235:genetics; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1