Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.
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.
Chen
Andrew C H
AC
Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Manz
Niklas
N
Tang
Yongqiang
Y
Rangaswamy
Madhavi
M
Almasy
Laura
L
Kuperman
Samuel
S
Nurnberger
John
J
O'Connor
Sean J
SJ
Edenberg
Howard J
HJ
Schuckit
Marc A
MA
Tischfield
Jay
J
Foroud
Tatiana
T
Bierut
Laura J
LJ
Rohrbaugh
John
J
Rice
John P
JP
Goate
Alison
A
Hesselbrock
Victor
V
Porjesz
Bernice
B
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
D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1