Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder

نویسندگان

  • 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
چکیده

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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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2012