Journal article
Myelination-related genes are associated with decreased white matter integrity in schizophrenia
European journal of human genetics : EJHG, Vol.24(3), pp.381-386
03/2016
DOI: 10.1038/ejhg.2015.120
PMCID: PMC4757770
PMID: 26014434
Abstract
Disruptions in white matter (WM) tract structures have been implicated consistently in the pathophysiology of schizophrenia. Global WM integrity--as measured by fractional anisotropy (FA)--is highly heritable and may provide a good endophenotype for genetic studies of schizophrenia. WM abnormalities in schizophrenia are not localized to one specific brain region but instead reflect global low-level decreases in FA coupled with focal abnormalities. In this study, we sought to investigate whether functional gene sets associated with schizophrenia are also associated with WM integrity. We analyzed FA and genetic data from the Mind Research Network Clinical Imaging Consortium to study the effect of multiple oligodendrocyte gene sets on schizophrenia and WM integrity using a functional gene set analysis in 77 subjects with schizophrenia and 104 healthy controls. We found that a gene set involved in myelination was significantly associated with schizophrenia and FA. This gene set includes 17 genes that are expressed in oligodendrocytes and one neuronal gene (NRG1) that is known to regulate myelination. None of the genes within the gene set were associated with schizophrenia or FA individually, suggesting that no single gene was driving the association of the gene set. Our findings support the hypothesis that multiple genetic variants in myelination-related genes contribute to the observed correlation between schizophrenia and decreased WM integrity as measured by FA.
Details
- Title: Subtitle
- Myelination-related genes are associated with decreased white matter integrity in schizophrenia
- Creators
- Ivan Chavarria-Siles - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USATonya White - Department of Radiology, Erasmus Medical Center, Rotterdam, The NetherlandsChristiaan de Leeuw - Department of Complex Trait Genetics, VU University Medical Center, Amsterdam, The NetherlandsAndrea Goudriaan - Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The NetherlandsEsther Lips - Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The NetherlandsStefan Ehrlich - Department of Child and Adolescent Psychiatry, TU Dresden, GermanyJessica A Turner - The Mind Research Network, Albuquerque, NM, USAVince D Calhoun - Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USARandy L Gollub - Departments of Psychiatry and Radiology, Massachusetts General Hospital, Boston, MA, USAVincent A Magnotta - Department of Radiology, The University of Iowa Carver College of Medicine, Iowa City, IA, USABeng-Choon Ho - Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USAAugust B Smit - Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The NetherlandsMark H G Verheijen - Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The NetherlandsDanielle Posthuma - Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands
- Resource Type
- Journal article
- Publication Details
- European journal of human genetics : EJHG, Vol.24(3), pp.381-386
- Publisher
- England
- DOI
- 10.1038/ejhg.2015.120
- PMID
- 26014434
- PMCID
- PMC4757770
- ISSN
- 1018-4813
- eISSN
- 1476-5438
- Grant note
- K08 MH068540 / NIMH NIH HHS R01 EB005846 / NIBIB NIH HHS P20 DA024196 / NIDA NIH HHS R01 MH060662 / NIMH NIH HHS MH060662 / NIMH NIH HHS P20DA024196 / NIDA NIH HHS
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984051731402771
Metrics
21 Record Views