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Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.


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.

SUBMITTER: de Leeuw C 

PROVIDER: S-EPMC4613465 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.

de Leeuw Christiaan C   Goudriaan Andrea A   Smit August B AB   Yu Dongmei D   Mathews Carol A CA   Scharf Jeremiah M JM   Verheijen Mark H G MH   Posthuma Danielle D  

European journal of human genetics : EJHG 20150304 11


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  ...[more]

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