title: Support of the histaminergic hypothesis in Tourette syndrome: association of the histamine decarboxylase gene in a large sample of families.
abstract: BACKGROUND
  Gilles de la Tourette Syndrome is a neurodevelopmental disorder that is caused by the interaction of environment with a complex genetic background. The genetic etiology of the disorder remains, so far, elusive, although multiple promising leads have been recently reported. The recent implication of the histamine decarboxylase (HDC) gene, the key enzyme in histamine production, raises the intriguing hypothesis of a possible role of histaminergic dysfunction leading to TS onset.
  
  
  METHODS
  Following up on the finding of a nonsense mutation in a single family with TS, we investigated variation across the HDC gene for association with TS. As a result of a collaborative international effort, we studied a large sample of 520 nuclear families originating from seven European populations (Greek, Hungarian, Italian, Polish, German, Albanian, Spanish) as well as a sample collected in Canada.
  
  
  CONCLUSIONS
  Interrogating 12 tagging SNPs (tSNP) across the HDC region, we find strong over-transmission of alleles at two SNPs (rs854150 and rs1894236) in the complete sample, as well as a statistically significant associated haplotypes. Analysis of individual populations also reveals signals of association in the Canadian, German and Italian samples. Our results provide strong support for the histaminergic hypothesis in TS etiology and point to a possible role of histamine pathways in neuronal development.
authors.affiliation: Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece.
authors.forename: Iordanis
authors.initials: I
authors.lastname: Karagiannidis
authors.forename: Sandra
authors.initials: S
authors.lastname: Dehning
authors.forename: Paul
authors.initials: P
authors.lastname: Sandor
authors.forename: Zsanett
authors.initials: Z
authors.lastname: Tarnok
authors.forename: Renata
authors.initials: R
authors.lastname: Rizzo
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wolanczyk
authors.forename: Marcos
authors.initials: M
authors.lastname: Madruga-Garrido
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Gerd
authors.initials: G
authors.lastname: Lehmkuhl
authors.forename: Luca
authors.initials: L
authors.lastname: Farkas
authors.forename: Peter
authors.initials: P
authors.lastname: Nagy
authors.forename: Urszula
authors.initials: U
authors.lastname: Szymanska
authors.forename: Zachos
authors.initials: Z
authors.lastname: Anastasiou
authors.forename: Vasileios
authors.initials: V
authors.lastname: Stathias
authors.forename: Christos
authors.initials: C
authors.lastname: Androutsos
authors.forename: Vaia
authors.initials: V
authors.lastname: Tsironi
authors.forename: Anastasia
authors.initials: A
authors.lastname: Koumoula
authors.forename: Csaba
authors.initials: C
authors.lastname: Barta
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Pablo
authors.initials: P
authors.lastname: Mir
authors.forename: Norbert
authors.initials: N
authors.lastname: Müller
authors.forename: Cathy
authors.initials: C
authors.lastname: Barr
authors.forename: Peristera
authors.initials: P
authors.lastname: Paschou
mesh_terms: D015331:Cohort Studies; D056726:Genetic Association Studies; D006239:Haplotypes; D006640:Histidine Decarboxylase / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D005879:Tourette Syndrome / Q000201:enzymology / Q000235:genetics*
chemical_list: D006640:Histidine Decarboxylase
keywords: Complex traits; Genetics; Other Psychiatry; Psychiatry