Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder.
<h4>Background</h4>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 neurotra...
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2012
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oai:doaj.org-article:276ac9b10ca449b19630d103d87b9fa92021-11-18T07:17:21ZGender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder.1932-620310.1371/journal.pone.0037651https://doaj.org/article/276ac9b10ca449b19630d103d87b9fa92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22662185/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Heike WeberClaus Jürgen ScholzKatharina DomschkeChristian BaumannBenedikt KlaukeChristian P JacobWolfgang MaierJürgen FritzeBorwin BandelowPeter Michael ZwanzgerThomas LangLydia FehmAndreas StröhleAlfons HammAlexander L GerlachGeorg W AlpersTilo KircherHans-Ulrich WittchenVolker AroltPaul PauliJürgen DeckertAndreas ReifPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37651 (2012) |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. |
| description |
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
| format |
article |
| 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 |
| author_facet |
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 |
| author_sort |
Heike Weber |
| title |
Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. |
| title_short |
Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. |
| title_full |
Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. |
| title_fullStr |
Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. |
| title_full_unstemmed |
Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder. |
| title_sort |
gender differences in associations of glutamate decarboxylase 1 gene (gad1) variants with panic disorder. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/276ac9b10ca449b19630d103d87b9fa9 |
| work_keys_str_mv |
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