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.