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Support of the histaminergic hypothesis in Tourette Syndrome: association of the histamine decarboxylase gene in a large sample of families
  1. Iordanis Karagiannidis1,
  2. Sandra Dehning2,
  3. Paul Sandor3,
  4. Zsanett Tarnok4,
  5. Renata Rizzo5,
  6. Tomasz Wolanczyk6,
  7. Marcos Madruga-Garrido7,
  8. Johannes Hebebrand8,
  9. Markus M Nöthen9,
  10. Gerd Lehmkuhl10,
  11. Luca Farkas4,
  12. Peter Nagy4,
  13. Urszula Szymanska6,
  14. Zachos Anastasiou1,
  15. Vasileios Stathias1http://orcid.org/0000-0003-1986-5947,
  16. Christos Androutsos11,
  17. Vaia Tsironi11,
  18. Anastasia Koumoula11,
  19. Csaba Barta12,
  20. Peter Zill2,
  21. Pablo Mir7,13,
  22. Norbert Müller2,
  23. Cathy Barr3,
  24. Peristera Paschou1
  1. 1Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece
  2. 2Department of Psychiatry, Ludwig-Maximilians-University Munich, Munich, Germany
  3. 3Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada
  4. 4Vadaskert Clinic for Child and Adolescent Psychiatry, Budapest, Hungary
  5. 5Materno-Infantile and Radiological Science Department, University of Catania, Catania, Italy
  6. 6Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland
  7. 7Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica/Sección de Neuropediatría, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
  8. 8Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany
  9. 9Department of Genomics, Life and Brain Center, Institute for Human Genetics, University of Bonn, Bonn, Germany
  10. 10Department of Child and Adolescent, Psychiatry of the University of Cologne, Cologne, Germany
  11. 11Child and Adolescent Psychiatry Clinic, Sismanoglio General Hospital of Attica, Athens, Greece
  12. 12Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary
  13. 13Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Seville, Spain
  1. Correspondence to Dr Peristera Paschou, Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli 68100, Greece, ppaschou{at}mbg.duth.gr

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.

Results and 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.

  • Psychiatry
  • Other Psychiatry
  • Genetics
  • Complex traits

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