Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder.
BACKGROUND
Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females.


RESULTS
Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score.


CONCLUSIONS
The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. Weber_H2@klinik.uni-wuerzburg.de
Heike
H
Weber
Claus Jürgen
CJ
Scholz
Katharina
K
Domschke
Christian
C
Baumann
Benedikt
B
Klauke
Christian P
CP
Jacob
Wolfgang
W
Maier
Jürgen
J
Fritze
Borwin
B
Bandelow
Peter Michael
PM
Zwanzger
Thomas
T
Lang
Lydia
L
Fehm
Andreas
A
Ströhle
Alfons
A
Hamm
Alexander L
AL
Gerlach
Georg W
GW
Alpers
Tilo
T
Kircher
Hans-Ulrich
HU
Wittchen
Volker
V
Arolt
Paul
P
Pauli
Jürgen
J
Deckert
Andreas
A
Reif
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1