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

• G.A.M. Blokland ^[1] ; N. Maleki ^[2] ; J. Jovicich ^[3] ; R.I. Mesholam-Gately ^[4] ; L.E. DeLisi ^[17] ; J.A. Turner ^[5] ; M.E. Shenton ^[18] ; A.N. Voineskos ^[6] ; R.S. Kahn ^[19] ; J.L. Roffman ^[7] ; D.J. Holt ^[7] ; S. Ehrlich ^[8] ; Z. Kikinis ^[18] ; P. Dazzan ^[20] ; R.M. Murray ^[20] ; J. Lee ^[21] ; K. Sim ^[21] ; M. Lam ^[9] ; S.M.C. de Zwarte ^[19] ; E. Walton ^[10] ; S. Kelly ^[11] ; M.M. Picchioni ^[20] ; E. Bramon ^[20] ; N. Makris ^[2] ; A.S. David ^[12] ; V. Mondelli ^[20] ; A.A.T.S. Reinders ^[20] ; E. Oykhman ^[4] ; D.W. Morris ^[13] ; M. Gill ^[11] ; A.P. Corvin ^[11] ; W. Cahn ^[19] ; N. Ho ^[21] ; J. Liu ^[22] ; R.L. Gollub ^[2] ; D.S. Manoach ^[2] ; V.D. Calhoun ^[23] ; S.R. Sponheim ^[14] ; S.L. Buka ^[15] ; S. Cherkerzian ^[7] ; H.W. Thermenos ^[4] ; E.W. Dickie ^[6] ; S. Ciufolini ^[20] ; Reis Marques ^[20] ; N.A. Crossley ^[20] ; S.M. Purcell ^[18] ; J.W. Smoller ^[2] ; N.E.M. van Haren ^[24] ; T. Toulopoulou ^[16] ; G. Donohoe ^[13] ; J.M. Goldstein ^[7] ; M.S. Keshavan ^[4] ; T.L. Petryshen ^[2] ; E.C. del Re ^[4]
  1. [1] Maastricht University

     Maastricht University

     Países Bajos

     
  2. [2] Massachusetts General Hospital

     Massachusetts General Hospital

     City of Boston, Estados Unidos

     
  3. [3] University of Trento

     University of Trento

     Trento, Italia

     
  4. [4] Beth Israel Deaconess Medical Center

     Beth Israel Deaconess Medical Center

     City of Boston, Estados Unidos

     
  5. [5] Ohio State University

     Ohio State University

     City of Columbus, Estados Unidos

     
  6. [6] University of Toronto

     University of Toronto

     Canadá

     
  7. [7] Harvard Medical School

     Harvard Medical School

     City of Boston, Estados Unidos

     
  8. [8] Dresden University of Technology

     Dresden University of Technology

     Kreisfreie Stadt Dresden, Alemania

     
  9. [9] Broad Institute

     Broad Institute

     City of Cambridge, Estados Unidos

     
  10. [10] University of Bath

      University of Bath

      Reino Unido

      
  11. [11] Trinity College Dublin

      Trinity College Dublin

      Irlanda

      
  12. [12] University College London

      University College London

      Reino Unido

      
  13. [13] National University of Ireland

      National University of Ireland

      Irlanda

      
  14. [14] University of Minnesota

      University of Minnesota

      City of Minneapolis, Estados Unidos

      
  15. [15] Brown University

      Brown University

      City of Providence, Estados Unidos

      
  16. [16] Bilkent University

      Bilkent University

      Turquía

      
  17. [17] Cambridge Health Alliance, Cambridge, MA, United States
  18. [18] Brigham and Women's Hospital, Boston, MA, United States
  19. [19] University Medical Centre Utrecht
  20. [20] Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom
  21. [21] Institute of Mental Health, Woodbridge Hospital, Singapore
  22. [22] Genome Institute, Singapore
  23. [23] Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State, Georgia Tech, Emory, Atlanta, GA, United States
  24. [24] Erasmus Medical Centre, Rotterdam

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• Localización: International journal of clinical and health psychology, ISSN 1697-2600, Vol. 24, Nº. 2, 2024, págs. 131-140
• Idioma: inglés
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• Resumen

  • 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.