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

G.A.M. Blokland; N. Maleki; J. Jovicich; R.I. Mesholam Gately; L.E. DeLisi; J.A. Turner; Martha Shenton; A.N. Voineskos; René S. Kahn; J.L. Roffman; D.J. Holt; S. Ehrlich; Z. Kikinis; P. Dazzan; R.M. Murray; J. Lee; K. Sim; Charlene L.M. Lam; S.M.C. de Zwarte; E. Walton; S. Kelly; M.M. Picchioni; E. Bramon; N. Makris; Anthony S. David; V. Mondelli; A.A.T.S. Reinders; E. Oykhman; D.W. Morris; M. Gill; A.P. Corvin; Wiepke Cahn; N. Ho; Jiao Liu; R.L. Gollub; D.S. Manoach; V. D. Calhoun; S.R. Sponheim; Stephen L. Buka; S. Cherkerzian; H.W. Thermenos; E.W. Dickie; S. Ciufolini; Reis Marques; N.A. Crossley; S.M. Purcell; Jordan W. Smoller; N.E.M. van Haren; T. Toulopoulou; G. Donohoe; J.M. Goldstein; M.S. Keshavan; T.L. Petryshen; Elisabetta C. del Re

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
Mostrar afiliaciones +
Localización: International journal of clinical and health psychology, ISSN 1697-2600, Vol. 24, Nº. 2, 2024, págs. 131-140
Idioma: inglés
DOI: 10.1016/j.ijchp.2024.100458
Enlaces
- Texto completo
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.
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