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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010map 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\u2010compulsive 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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The polymorphism rs3096140 in glial cell line\u2013derived neurotrophic factor gene (<jats:italic>GDNF)<\/jats:italic> was significant in the discovery cohort after correction (<jats:italic>P<\/jats:italic>\u2009=\u20091.5 \u00d7 10<jats:sup>\u22124<\/jats:sup>). 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 (<jats:italic>P<\/jats:italic>\u2009=\u20090.01). No association with any comorbidity was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As a conclusion, a common genetic variant in <jats:italic>GDNF<\/jats:italic> 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. \u00a9 2015 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.26279","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T20:38:44Z","timestamp":1434746324000},"page":"1115-1120","source":"Crossref","is-referenced-by-count":17,"title":["<i>GDNF<\/i> gene is associated with tourette syndrome in a family study"],"prefix":"10.1002","volume":"30","author":[{"given":"Ismael","family":"Huertas\u2010Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Unidad de Trastornos del Movimiento, Servicio de Neurolog\u00eda y Neurofisiolog\u00eda Cl\u00ednica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"G\u00f3mez\u2010Garre","sequence":"additional","affiliation":[{"name":"Unidad de 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