Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis
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.
|Persistent URL||dx.doi.org/10.1038/ejhg.2015.22, hdl.handle.net/1765/88513|
|Journal||European Journal of Human Genetics|
de Leeuw, C, Goudriaan, A, Smit, A.B, Yu, D, Mathews, C.A, Scharf, J.M, … Posthuma, D. (2015). Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis. European Journal of Human Genetics, 23(11), 1519–1522. doi:10.1038/ejhg.2015.22