Format

Send to

Choose Destination

See 1 citation found by title matching your search:

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

Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.

Author information

1
Department of Complex Trait Genetics, VU University Medical Center, Amsterdam, The Netherlands.
2
Institute for Computing and Information Sciences, Radboud University, Nijmegen, The Netherlands.
3
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
4
Psychiatric and Neurodevelopmental Genetics Unit, Departments of Psychiatry and Neurology, Center for Human Genetics Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
5
Department of Psychiatry, Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
6
Division of Cognitive and Behavioral Neurology, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
7
Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
8
Department of Child and Adolescent Psychiatry, Erasmus University Rotterdam, Sophia Child Hospital, Rotterdam, The Netherlands.

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.

PMID:
25735483
PMCID:
PMC4613465
DOI:
10.1038/ejhg.2015.22
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center