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Molecular Landscape of Tourette’s Disorder

Tourette’s disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. Yet, the molecular mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data...

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Autores principales: Widomska, Joanna, De Witte, Ward, Buitelaar, Jan K., Glennon, Jeffrey C., Poelmans, Geert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865021/
https://www.ncbi.nlm.nih.gov/pubmed/36674940
http://dx.doi.org/10.3390/ijms24021428
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author Widomska, Joanna
De Witte, Ward
Buitelaar, Jan K.
Glennon, Jeffrey C.
Poelmans, Geert
author_facet Widomska, Joanna
De Witte, Ward
Buitelaar, Jan K.
Glennon, Jeffrey C.
Poelmans, Geert
author_sort Widomska, Joanna
collection PubMed
description Tourette’s disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. 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 (‘cAMP-mediated signaling’ and ‘Endocannabinoid Neuronal Synapse Pathway’) 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.
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spelling pubmed-98650212023-01-22 Molecular Landscape of Tourette’s Disorder Widomska, Joanna De Witte, Ward Buitelaar, Jan K. Glennon, Jeffrey C. Poelmans, Geert Int J Mol Sci Article Tourette’s disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. 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 (‘cAMP-mediated signaling’ and ‘Endocannabinoid Neuronal Synapse Pathway’) 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. MDPI 2023-01-11 /pmc/articles/PMC9865021/ /pubmed/36674940 http://dx.doi.org/10.3390/ijms24021428 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Widomska, Joanna
De Witte, Ward
Buitelaar, Jan K.
Glennon, Jeffrey C.
Poelmans, Geert
Molecular Landscape of Tourette’s Disorder
title Molecular Landscape of Tourette’s Disorder
title_full Molecular Landscape of Tourette’s Disorder
title_fullStr Molecular Landscape of Tourette’s Disorder
title_full_unstemmed Molecular Landscape of Tourette’s Disorder
title_short Molecular Landscape of Tourette’s Disorder
title_sort molecular landscape of tourette’s disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865021/
https://www.ncbi.nlm.nih.gov/pubmed/36674940
http://dx.doi.org/10.3390/ijms24021428
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