Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder
2012 | journal article. A publication with affiliation to the University of Göttingen.
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Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder
Weber, H.; Scholz, C. J.; Domschke, K.; Baumann, C.; Klauke, B.; Jacob, C. P. & Maier, W. et al. (2012)
PLoS ONE, 7(5) art. e37651. DOI: https://doi.org/10.1371/journal.pone.0037651
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- Authors
- Weber, Heike; Scholz, Claus Juergen; Domschke, Katharina; Baumann, Christian; Klauke, Benedikt; Jacob, Christian P.; Maier, Wolfgang; Fritze, Juergen; Bandelow, Borwin; Zwanzger, Peter Michael; Lang, Thomas; Fehm, Lydia; Stroehle, Andreas; Hamm, Alfons; Gerlach, Alexander L.; Alpers, Georg W.; Kircher, Tilo T. J.; Wittchen, Hans-Ulrich; Arolt, Volker; Pauli, Paul; Deckert, Juergen; Reif, Andreas
- 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 genotypexgender 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 genotypexgender 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.
- Issue Date
- 2012
- Status
- published
- Publisher
- Public Library Science
- Journal
- PLoS ONE
- ISSN
- 1932-6203