Myelination-related genes are associated with decreased white matter integrity in schizophrenia

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Ivan Chavarria-Siles - , Vrije Universiteit Amsterdam (VU), Icahn School of Medicine at Mount Sinai (Author)
  • Tonya White - , Erasmus University Rotterdam (Author)
  • Christiaan De Leeuw - , Vrije Universiteit Amsterdam (VU) (Author)
  • Andrea Goudriaan - , Vrije Universiteit Amsterdam (VU) (Author)
  • Esther Lips - , Vrije Universiteit Amsterdam (VU) (Author)
  • Stefan Ehrlich - , Department of Child and Adolescent Psychiatry and Psychotherapy, Massachusetts General Hospital (Author)
  • Jessica A. Turner - , Georgia State University, The Mind Research Network (Author)
  • Vince D. Calhoun - , The Mind Research Network, University of New Mexico (Author)
  • Randy L. Gollub - , Massachusetts General Hospital (Author)
  • Vincent A. Magnotta - , University of Iowa (Author)
  • Eng Choon Ho - , University of Iowa (Author)
  • August B. Smit - , Vrije Universiteit Amsterdam (VU) (Author)
  • Mark H.G. Verheijen - , Vrije Universiteit Amsterdam (VU) (Author)
  • Danielle Posthuma - , Vrije Universiteit Amsterdam (VU), Erasmus University Rotterdam (Author)

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

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalEuropean Journal of Human Genetics
Volume24
Issue number3
Publication statusPublished - 1 Mar 2016
Peer-reviewedYes

External IDs

researchoutputwizard legacy.publication#72937
Scopus 84958118247
PubMed 26014434
ORCID /0000-0003-2132-4445/work/159605878

Keywords

ASJC Scopus subject areas