UCSF

Tourette Syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genomewide 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 analyses using expert curated sets of brain‐expressed genes in the current largest available Tourette Syndrome genome‐wide association dataset, involving 1285 cases and 4964 controls. The gene‐sets included specific synaptic, astrocytic, oliogodendrocyte 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.