Association study between GABA receptor genes and anxiety spectrum disorders.
BACKGROUND
Human anxiety disorders are complex diseases with relatively unknown etiology. Dysfunction of the Gamma-aminobutyric acid (GABA) system has been implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. In this investigation, we explored four GABA receptor genes for their possible associations with genetic risk for anxiety disorders and depression.


METHODS
Our study sample consisted of 589 cases and 539 controls selected from a large population-based twin registry based upon a latent genetic risk factor shared by several anxiety disorders, major depression, and neuroticism. We subjected these to a two-stage protocol, in which all candidate genetic markers were screened for association in stage 1 (N=376), the positive results of which were tested for replication in stage 2 (N=752). We analyzed data from 26 single nucleotide polymorphisms (SNPs) from four GABA receptor genes: GABRA2, GABRA3, GABRA6, and GABRG2.


RESULTS
Of the 26 SNPs genotyped in stage 1, we identified two markers in GABRA3 that met the threshold (P < or = .1) to be tested in stage 2. Phenotypic associations of these two markers failed to replicate in stage 2.


CONCLUSIONS
These findings suggest that common variation in the GABRA2, GABRA3, GABRA6, and GABRG2 genes does not play a major role in liability to anxiety spectrum disorders.
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia 23298-0126, USA.
Xuan
X
Pham
Cuie
C
Sun
Xiangning
X
Chen
Edwin J C G
EJ
van den Oord
Michael C
MC
Neale
Kenneth S
KS
Kendler
John M
JM
Hettema
D000328:Adult; D000483:Alleles; D001008:Anxiety Disorders / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009497:Neurotic Disorders / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D012042:Registries; D055815:Young Adult
C484841:GABRA2 protein, human; C546257:GABRA3 protein, human; C546171:GABRA6 protein, human; C546279:GABRG2 protein, human; D005819:Genetic Markers; D011963:Receptors, GABA-A