Shared genetic architecture between schizophrenia and subcortical brain susceptibility phenotypes
Yingying Xie1,2, Jiaojiao Du3, Yao Zhao4
1Department of Radiology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Schizophrenia (Heidelberg, Germany)
|July 7, 2026
Summary
This study reveals shared genetic links between schizophrenia and iron levels in brain regions like the nucleus accumbens. Findings suggest new therapeutic targets for schizophrenia by exploring brain iron regulation pathways.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia (SCZ) is a heritable neuropsychiatric disorder.
- Dysregulated brain iron in subcortical regions is implicated in SCZ pathophysiology.
Purpose of the Study:
- To systematically dissect the shared genetic architecture between SCZ and subcortical brain susceptibility phenotypes.
- To identify specific brain regions and genetic pathways involved in SCZ and iron regulation.
Main Methods:
- Integration of genome-wide association study (GWAS) data with quantitative susceptibility mapping (QSM) phenotypes across 16 subcortical regions.
- Utilized the MiXeR framework to quantify genetic overlap.
- Performed conditional and conjunction false discovery rate analyses to identify shared SNPs.
Main Results:
- Strongest genetic overlap between SCZ and QSM phenotypes was found in the nucleus accumbens.
- Identified 666 unique shared single nucleotide polymorphisms (SNPs).
- Functional annotation revealed enrichment in synaptic function and neuronal development pathways, with pronounced neuronal expression.
- Identified 89 significant expression-trait associations and 691 potential protein-drug pairs via virtual drug screening.
Conclusions:
- Provides novel insights into the interaction between subcortical brain iron regulation and SCZ.
- Highlights specific genetic pathways and potential therapeutic targets for SCZ and related conditions.
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