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. 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 WeberORCiDGND, Claus Jürgen Scholz, Katharina Domschke, Christian Baumann, Benedikt Klauke, Christian P. Jacob, Wolfgang Maier, Jürgen Fritze, Borwin Bandelow, Peter M. Zwanzger, Thomas Lang, Lydia Fehm, Andreas StröhleORCiDGND, Alfons Hamm, Alexander Gerlach, Georg W. Alpers, Tilo KircherORCiDGND, Hans-Ulrich Wittchen, Volker AroltORCiDGND, Paul Pauli, Jürgen DeckertORCiDGND, Andreas ReifORCiDGND
URN:urn:nbn:de:hebis:30:3-249955
DOI:https://doi.org/doi:10.1371/journal.pone.0037651
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/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:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/06/01
Volume:7
Issue:(5):e37651
Page Number:7
HeBIS-PPN:357339355
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0