MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Maastricht University
- Massachusetts General Hospital
- Harvard University
- Broad Institute of Harvard University and MIT
- University of Trento
- Ohio State University
- VA Medical Center
- University of Toronto
- Utrecht University
- King's College London (KCL)
- South London and Maudsley NHS Foundation Trust
- Singapore Institute of Mental Health
- Zucker Hillside Hospital
- University of Bath
- Trinity College Dublin
- Keck School of Medicine at University of Southern California
- University College London
- University of Galway
- Georgia Institute of Technology
- University of Minnesota System
- Brown University
- Icahn School of Medicine at Mount Sinai
- Erasmus University Rotterdam
- Bilkent University
- National and Kapodistrian University of Athens
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
Original language | English |
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Article number | 100458 |
Pages (from-to) | 1-12 |
Number of pages | 12 |
Journal | International journal of clinical and health psychology |
Volume | 24 |
Issue number | 2 |
Publication status | Published - 9 Apr 2024 |
Peer-reviewed | Yes |
External IDs
ORCID | /0000-0003-2132-4445/work/177360808 |
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Keywords
ASJC Scopus subject areas
Keywords
- Corpus callosum, Ephrin pathway, Lateral ventricles, MIR137, Polygenic risk score, Schizophrenia