Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

European Journal of Human Genetics : EJHG
Christiaan de LeeuwDanielle Posthuma

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.

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Citations

Jul 28, 2016·Frontiers in Neuroscience·Luca PagliaroliCsaba Barta
Dec 23, 2016·Brain : a Journal of Neurology·Ahmad Seif KanaanKirsten Müller-Vahl
Jan 9, 2016·F1000Research·Cheryl A Richards, Kevin J Black
Jan 20, 2021·Translational Psychiatry·Fotis TsetsosSamuel Zinner
Mar 2, 2021·Frontiers in Neuroscience·Gerald A MaguireShahriar SheikhBahaei
Mar 30, 2021·Frontiers in Psychiatry·Raymond A ClarkeValsamma Eapen
Oct 11, 2017·Progress in Neuro-psychopharmacology & Biological Psychiatry·Ronald KimKathryn J Reissner
Jun 8, 2021·Brain and Language·Ariana Z TurkShahriar SheikhBahaei

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