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Yet, the molecular mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data to compile a list of TD candidate genes, and we subsequently conducted tissue\/cell type specificity and functional enrichment analyses of this list. Using genomic data, we also investigated genetic sharing between TD and blood and cerebrospinal fluid (CSF) metabolite levels. Lastly, we built a molecular landscape of TD through integrating the results from these analyses with an extensive literature search to identify the interactions between the TD candidate genes\/proteins and metabolites. We found evidence for an enriched expression of the TD candidate genes in four brain regions and the pituitary. The functional enrichment analyses implicated two pathways (\u2018cAMP-mediated signaling\u2019 and \u2018Endocannabinoid Neuronal Synapse Pathway\u2019) and multiple biological functions related to brain development and synaptic transmission in TD etiology. Furthermore, we found genetic sharing between TD and the blood and CSF levels of 39 metabolites. The landscape of TD not only provides insights into the (altered) molecular processes that underlie the disease but, through the identification of potential drug targets (such as FLT3, NAALAD2, CX3CL1-CX3CR1, OPRM1, and HRH2), it also yields clues for developing novel TD treatments.<\/jats:p>","DOI":"10.3390\/ijms24021428","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T05:26:31Z","timestamp":1673414791000},"page":"1428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular Landscape of Tourette\u2019s Disorder"],"prefix":"10.3390","volume":"24","author":[{"given":"Joanna","family":"Widomska","sequence":"first","affiliation":[{"name":"Department of Cognitive Neuroscience, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ward","family":"De Witte","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-7757","authenticated-orcid":false,"given":"Jan K.","family":"Buitelaar","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-0422","authenticated-orcid":false,"given":"Jeffrey C.","family":"Glennon","sequence":"additional","affiliation":[{"name":"Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert","family":"Poelmans","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16097","DOI":"10.1038\/nrdp.2016.97","article-title":"Gilles de la Tourette syndrome","volume":"3","author":"Robertson","year":"2017","journal-title":"Nat. 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