1. MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.
- Author
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Blokland GAM, Maleki N, Jovicich J, Mesholam-Gately RI, DeLisi LE, Turner JA, Shenton ME, Voineskos AN, Kahn RS, Roffman JL, Holt DJ, Ehrlich S, Kikinis Z, Dazzan P, Murray RM, Lee J, Sim K, Lam M, de Zwarte SMC, Walton E, Kelly S, Picchioni MM, Bramon E, Makris N, David AS, Mondelli V, Reinders AATS, Oykhman E, Morris DW, Gill M, Corvin AP, Cahn W, Ho N, Liu J, Gollub RL, Manoach DS, Calhoun VD, Sponheim SR, Buka SL, Cherkerzian S, Thermenos HW, Dickie EW, Ciufolini S, Reis Marques T, Crossley NA, Purcell SM, Smoller JW, van Haren NEM, Toulopoulou T, Donohoe G, Goldstein JM, Keshavan MS, Petryshen TL, and Del Re EC
- 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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for International Journal of Clinical and Health Psychology and was not involved in the editorial review or the decision to publish this article., (© 2024 The Author(s).)
- Published
- 2024
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