title: Myelination-related genes are associated with decreased white matter integrity in schizophrenia.
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.
authors.affiliation: Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.|Department of Complex Trait Genetics, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Chavarria-Siles
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Tonya
authors.initials: T
authors.lastname: White
authors.affiliation: Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.|Department of Complex Trait Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Christiaan
authors.initials: C
authors.lastname: de Leeuw
authors.affiliation: Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Goudriaan
authors.affiliation: Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Lips
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA.|Department of Child and Adolescent Psychiatry, TU Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Department of Psychology and Neuroscience Institute, Georgia State University, Atlanta, GA, USA.|The Mind Research Network, Albuquerque, NM, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Turner
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.|Department of Psychiatry, University of New Mexico, New Mexico, NM, USA.|Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Vince D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA.|Departments of Psychiatry and Radiology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.affiliation: Department of Radiology, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Magnotta
authors.affiliation: Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Beng-Choon
authors.initials: BC
authors.lastname: Ho
authors.affiliation: Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Molecular and Cellular Neurobiology, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Mark H G
authors.initials: MH
authors.lastname: Verheijen
authors.affiliation: Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.|Department of Complex Trait Genetics, VU University Medical Center, Amsterdam, The Netherlands.|Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
mesh_terms: D000328:Adult; D016880:Anisotropy; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009186:Myelin Sheath / Q000235:genetics* / Q000473:pathology*; D009836:Oligodendroglia / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D066127:White Matter / Q000473:pathology*