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Hemispheric Asymmetry in the Genetic Overlap between Schizophrenia and White Matter Microstructure
Yujie Zhang1, Mengge Liu1, Shaoying Wang1
1Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Cyborg and Bionic Systems (Washington, D.C.)
|January 12, 2026
Summary
Schizophrenia shares significant genetic overlap with white matter microstructure, revealing lateralized brain patterns and neurodevelopmental links. This study enhances understanding of the genetic basis for brain abnormalities in schizophrenia.
Area of Science:
- Neurogenetics
- Brain Imaging
- Psychiatric Disorders
Background:
- White matter microstructure is crucial for neural communication and is genetically influenced.
- Schizophrenia is associated with disruptions in white matter, but its shared genetic architecture with white matter microstructure is not fully understood.
- Previous genome-wide association studies (GWAS) identified numerous schizophrenia loci, but their overlap with white matter traits requires further investigation.
Purpose of the Study:
- To investigate the genetic overlap between schizophrenia and white matter microstructure using multidimensional diffusion tensor imaging (DTI) metrics.
- To explore hemispheric distinctions in the shared genetic architecture.
- To identify specific genetic loci and their functional relevance in neurodevelopment.
Main Methods:
- Employed the conditional/conjunctional false discovery rate (cond/conjFDR) approach for genetic overlap analysis.
- Utilized large-scale GWAS datasets for schizophrenia and white matter microstructure (fractional anisotropy, mean diffusivity, eigenvalues) in individuals of European ancestry.
- Conducted functional and validation analyses for shared genetic loci, including hemisphere-specific analyses.
Main Results:
- Identified 435 shared genetic loci between schizophrenia and white matter microstructure, with 154 exclusive to 3 eigenvalues.
- Revealed lateralized genetic patterns, with significant left-specific (25.5%-34.4%) and right-specific (23.9%-33.7%) loci.
- Enrichment analysis linked shared loci to nervous system and central nervous system development.
Conclusions:
- Demonstrated a complex, shared genetic architecture between schizophrenia and white matter microstructure.
- Highlighted the importance of hemispheric genetic asymmetry in brain structure.
- Emphasized the value of multidimensional DTI metrics in understanding the genetic basis of brain abnormalities in schizophrenia.
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