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 enzym
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.
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Author:Heike Weber, Claus Jürgen Scholz, Katharina Domschke, Christian Baumann, Benedikt Klauke, Christian P. Jacob, Wolfgang Maier, Jürgen Fritze, Borwin Bandelow, Peter Michael Zwanzger, Thomas Lang, Lydia Fehm, Andreas Ströhle, Alfons Hamm, Alexander L. Gerlach, Georg W. Alpers, Tilo Kircher, Hans-Ulrich Wittchen, Volker Arolt, Paul Pauli, Jürgen Deckert, Andreas Reif
URN:urn:nbn:de:hebis:30:3-249955
DOI:http://dx.doi.org/doi:10.1371/journal.pone.0037651
ISSN:1932-6203
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22662185
Parent Title (English):PLoS one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2012/05/25
Date of first Publication:2012/05/25
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/06/01
Volume:7
Issue:(5): e37651
Pagenumber:7
First Page:1
Last Page:7
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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