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PLoS One. 2012;7(5):e37651. doi: 10.1371/journal.pone.0037651. Epub 2012 May 25.

Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder.

Author information

  • 1Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. Weber_H2@klinik.uni-wuerzburg.de

Abstract

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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/SIGNIFICANCE:

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.

PMID:
22662185
[PubMed - indexed for MEDLINE]
PMCID:
PMC3360757
Free PMC Article
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