Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

Tourette Syndrome Association International Consortium for Genetics

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1519-1522
Number of pages4
JournalEuropean Journal of Human Genetics
Volume23
Issue number11
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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