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- Title
Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.
- Authors
de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Verheijen, Mark H G; Posthuma, Danielle
- Abstract
Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis.
- Subjects
TOURETTE syndrome; ASTROCYTES; CELL physiology; PATHOLOGICAL physiology; GENE expression; METABOLIC regulation; GENETICS
- Publication
European Journal of Human Genetics, 2015, Vol 23, Issue 11, p1519
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/ejhg.2015.22