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GDNF gene is associated with tourette syndrome in a family study.

Authors :
Huertas-Fernández, Ismael
Gómez-Garre, Pilar
Madruga-Garrido, Marcos
Bernal-Bernal, Inmaculada
Bonilla-Toribio, Marta
Martín-Rodríguez, Juan Francisco
Cáceres-Redondo, María Teresa
Vargas-González, Laura
Carrillo, Fátima
Pascual, Alberto
Tischfield, Jay A.
King, Robert A.
Heiman, Gary A.
Mir, Pablo
Source :
Movement Disorders; Jul2015, Vol. 30 Issue 8, p1115-1120, 7p
Publication Year :
2015

Abstract

Background Tourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive-compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome. Methods We genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine-map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive-compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls). Results The polymorphism rs3096140 in glial cell line-derived neurotrophic factor gene ( GDNF) was significant in the discovery cohort after correction ( P = 1.5 × 10<superscript>−4</superscript>). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort ( P = 0.01). No association with any comorbidity was found. Conclusions As a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08853185
Volume :
30
Issue :
8
Database :
Complementary Index
Journal :
Movement Disorders
Publication Type :
Academic Journal
Accession number :
108354639
Full Text :
https://doi.org/10.1002/mds.26279