MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • G. A.M. Blokland - , Maastricht University, Massachusetts General Hospital, Harvard University, Broad Institute of Harvard University and MIT (Autor:in)
  • N. Maleki - , Massachusetts General Hospital, Harvard University (Autor:in)
  • J. Jovicich - , Università degli Studi di Trento (Autor:in)
  • R. I. Mesholam-Gately - , Harvard University (Autor:in)
  • L. E. DeLisi - , Harvard University (Autor:in)
  • J. A. Turner - , Ohio State University (Autor:in)
  • M. E. Shenton - , Harvard University, US Department of Veterans Affairs (Autor:in)
  • A. N. Voineskos - , University of Toronto (Autor:in)
  • R. S. Kahn - , Utrecht University (Autor:in)
  • J. L. Roffman - , Massachusetts General Hospital, Harvard University (Autor:in)
  • D. J. Holt - , Massachusetts General Hospital, Harvard University (Autor:in)
  • S. Ehrlich - , Psychosoziale Medizin und Entwicklungsneurowissenschaften (Autor:in)
  • Z. Kikinis - , Harvard University (Autor:in)
  • P. Dazzan - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • R. M. Murray - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • J. Lee - , Singapore Institute of Mental Health (Autor:in)
  • K. Sim - , Singapore Institute of Mental Health (Autor:in)
  • M. Lam - , Broad Institute of Harvard University and MIT, Singapore Institute of Mental Health, Massachusetts General Hospital, Zucker Hillside Hospital (Autor:in)
  • S. M.C. de Zwarte - , Utrecht University (Autor:in)
  • E. Walton - , University of Bath (Autor:in)
  • S. Kelly - , Trinity College Dublin, Keck School of Medicine at University of Southern California (Autor:in)
  • M. M. Picchioni - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • E. Bramon - , King's College London (KCL), South London and Maudsley NHS Foundation Trust, University College London (Autor:in)
  • N. Makris - , Massachusetts General Hospital, Harvard University (Autor:in)
  • A. S. David - , University College London (Autor:in)
  • V. Mondelli - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • A. A.T.S. Reinders - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • E. Oykhman - , Harvard University (Autor:in)
  • D. W. Morris - , University of Galway (Autor:in)
  • M. Gill - , Trinity College Dublin (Autor:in)
  • A. P. Corvin - , Trinity College Dublin (Autor:in)
  • W. Cahn - , Utrecht University (Autor:in)
  • N. Ho - , Singapore Institute of Mental Health (Autor:in)
  • J. Liu - , Agency for Science, Technology and Research, Singapore (Autor:in)
  • R. L. Gollub - , Massachusetts General Hospital, Harvard University (Autor:in)
  • D. S. Manoach - , Massachusetts General Hospital, Harvard University (Autor:in)
  • V. D. Calhoun - , Georgia Institute of Technology (Autor:in)
  • S. R. Sponheim - , University of Minnesota System (Autor:in)
  • S. L. Buka - , Brown University (Autor:in)
  • S. Cherkerzian - , Harvard University (Autor:in)
  • H. W. Thermenos - , Massachusetts General Hospital, Harvard University (Autor:in)
  • E. W. Dickie - , University of Toronto (Autor:in)
  • S. Ciufolini - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • T. Reis Marques - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • N. A. Crossley - , King's College London (KCL), South London and Maudsley NHS Foundation Trust (Autor:in)
  • S. M. Purcell - , Harvard University, Broad Institute of Harvard University and MIT, Icahn School of Medicine at Mount Sinai (Autor:in)
  • J. W. Smoller - , Massachusetts General Hospital, Harvard University, Broad Institute of Harvard University and MIT (Autor:in)
  • N. E.M. van Haren - , Erasmus University Rotterdam, Utrecht University (Autor:in)
  • T. Toulopoulou - , Bilkent University, National and Kapodistrian University of Athens, Icahn School of Medicine at Mount Sinai (Autor:in)
  • G. Donohoe - , Trinity College Dublin, University of Galway (Autor:in)

Abstract

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137’s essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Details

OriginalspracheEnglisch
Aufsatznummer100458
Seiten (von - bis)1-12
Seitenumfang12
FachzeitschriftInternational journal of clinical and health psychology
Jahrgang24
Ausgabenummer2
PublikationsstatusVeröffentlicht - 9 Apr. 2024
Peer-Review-StatusJa

Externe IDs

ORCID /0000-0003-2132-4445/work/177360808

Schlagworte

ASJC Scopus Sachgebiete

Schlagwörter

  • Corpus callosum, Ephrin pathway, Lateral ventricles, MIR137, Polygenic risk score, Schizophrenia