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

Blokland, GAM; Maleki, N; Jovicich, J; Mesholam-Gately, RI; DeLisi, LE; Turner, JA; Shenton, ME; ... del Re, EC; + view all (2024) MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume. International Journal of Clinical and Health Psychology , 24 (2) , Article 100458. 10.1016/j.ijchp.2024.100458. Green open access

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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.

Type: Article
Title: MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijchp.2024.100458
Publisher version: http://dx.doi.org/10.1016/j.ijchp.2024.100458
Language: English
Additional information: © 2024 The Author(s). Published by Elsevier B.V. under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Corpus callosum, Lateral ventricles, MIR137, Polygenic risk score, Schizophrenia, Ephrin pathway
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Institute of Mental Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10190938
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