| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 7, Iss 5, p e37651 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0037651 |
| Popis: |
BackgroundPanic 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 findingsNineteen 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/significanceThe 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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