Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

Eur J Hum Genet. 2015 Nov;23(11):1519-22. doi: 10.1038/ejhg.2015.22. Epub 2015 Mar 4.

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.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Glutamic Acid
  • Humans
  • Microglia / metabolism
  • Microglia / pathology*
  • Neurons / metabolism
  • Neurons / pathology
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology
  • Tourette Syndrome / genetics*
  • Tourette Syndrome / metabolism
  • Tourette Syndrome / physiopathology

Substances

  • Glutamic Acid