The GABA transporter 1 (SLC6A1): a novel candidate gene for anxiety disorders.
Recent evidence suggests that the GABA transporter 1 (GAT-1; SLC6A1) plays a role in the pathophysiology and treatment of anxiety disorders. In order to understand the impact of genetic variation within SLC6A1 on pathological anxiety, we performed a case-control association study with anxiety disorder patients with and without syndromal panic attacks. Using the method of sequential addition of cases, we found that polymorphisms in the 5' flanking region of SLC6A1 are highly associated with anxiety disorders when considering the severity of syndromal panic attacks as phenotype covariate. Analysing the effect size of the association, we observed a constant increase in the odds ratio for disease susceptibility with an increase in panic severity (OR approximately 2.5 in severely affected patients). Nominally significant association effects were observed considering the entire patient sample. These data indicate a high load of genetic variance within SLC6A1 on pathological anxiety and highlight GAT-1 as a promising target for treatment of anxiety disorders with panic symptoms.
Thoeringer
C K
CK
Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. thoeringer@mpipsykl.mpg.de
Ripke
S
S
Unschuld
P G
PG
Lucae
S
S
Ising
M
M
Bettecken
T
T
Uhr
M
M
Keck
M E
ME
Mueller-Myhsok
B
B
Holsboer
F
F
Binder
E B
EB
Erhardt
A
A
D000328:Adult; D001008:Anxiety Disorders / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
D050485:GABA Plasma Membrane Transport Proteins; C493413:SLC6A1 protein, human